1194:
bone tissues range from soft to stiff. The transduction of the stem cells into these cells types is not directed solely by chemokine cues and cell to cell signaling. The elasticity of the microenvironment can also affect the differentiation of mesenchymal stem cells (MSCs which originate in bone marrow.) When MSCs are placed on substrates of the same stiffness as brain, muscle and bone ECM, the MSCs take on properties of those respective cell types. Matrix sensing requires the cell to pull against the matrix at focal adhesions, which triggers a cellular mechano-transducer to generate a signal to be informed what force is needed to deform the matrix. To determine the key players in matrix-elasticity-driven lineage specification in MSCs, different matrix microenvironments were mimicked. From these experiments, it was concluded that focal adhesions of the MSCs were the cellular mechano-transducer sensing the differences of the matrix elasticity. The non-muscle myosin IIa-c isoforms generates the forces in the cell that lead to signaling of early commitment markers. Nonmuscle myosin IIa generates the least force increasing to non-muscle myosin IIc. There are also factors in the cell that inhibit non-muscle myosin II, such as
1175:. In culture, Bmi1 mediates the Hedgehog pathway's ability to promote human mammary stem cell self-renewal. In both humans and mice, researchers showed Bmi1 to be highly expressed in proliferating immature cerebellar granule cell precursors. When Bmi1 was knocked out in mice, impaired cerebellar development resulted, leading to significant reductions in postnatal brain mass along with abnormalities in motor control and behavior. A separate study showed a significant decrease in neural stem cell proliferation along with increased astrocyte proliferation in Bmi null mice.
484:
34:
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1198:. This makes the cell effectively blind to the surrounding matrix. Researchers have achieved some success in inducing stem cell-like properties in HEK 239 cells by providing a soft matrix without the use of diffusing factors. The stem-cell properties appear to be linked to tension in the cells' actin network. One identified mechanism for matrix-induced differentiation is tension-induced proteins, which remodel chromatin in response to mechanical stretch. The RhoA pathway is also implicated in this process.
1055:, respectively. The acetyl group prevents Lysine's association with the negatively charged DNA backbone. Methylation is not as straightforward, as neither methylation nor demethylation consistently correlate with either gene activation or repression. However, certain methylations have been repeatedly shown to either activate or repress genes. The trimethylation of lysine 4 on histone 3 (H3K4Me3) is associated with gene activation, whereas trimethylation of lysine 27 on histone 3 represses genes
998:-mediated methylation of cytosine residues in CpG dinucleotides maintains heritable repression by controlling DNA accessibility. The majority of CpG sites in embryonic stem cells are unmethylated and appear to be associated with H3K4me3-carrying nucleosomes. Upon differentiation, a small number of genes, including OCT4 and NANOG, are methylated and their promoters repressed to prevent their further expression. Consistently, DNA methylation-deficient embryonic stem cells rapidly enter
661:
1095:, and the majority of current knowledge about the subject consists of speculations on plausible candidate regulators of epigenetic remodeling. We will first discuss several major candidates thought to be involved in the induction and maintenance of both embryonic stem cells and their differentiated progeny, and then turn to one example of specific signaling pathways in which more direct evidence exists for its role in epigenetic change.
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613:
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acquires enzymatic activity. The receptor then catalyzes reactions that phosphorylate other proteins, activating them. A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in the target cell. Cells and tissues can vary in competence, their ability to respond to external signals.
893:. Second, the mechanisms of reprogramming (and by extension, differentiation) are very complex and cannot be easily duplicated, as seen by the significant number of differentially methylated regions between ES and iPS cell lines. Now that these two points have been established, we can examine some of the epigenetic mechanisms that are thought to regulate cellular differentiation.
1152:
Direct modulation of gene expression through modification of transcription factors plays a key role that must be distinguished from heritable epigenetic changes that can persist even in the absence of the original environmental signals. Only a few examples of signaling pathways leading to epigenetic changes that alter cell fate currently exist, and we will focus on one of them.
45:
3629:
1047:. The epigenetic processes of histone methylation and acetylation, and their inverses demethylation and deacetylation primarily account for these changes. The effects of acetylation and deacetylation are more predictable. An acetyl group is either added to or removed from the positively charged Lysine residues in histones by enzymes called
986:) and promote gene activation through histone acetylation. PcG and TrxG complexes engage in direct competition and are thought to be functionally antagonistic, creating at differentiation and development-promoting loci what is termed a "bivalent domain" and rendering these genes sensitive to rapid induction or repression.
1193:
In order to fulfill the purpose of regenerating a variety of tissues, adult stems are known to migrate from their niches, adhere to new extracellular matrices (ECM) and differentiate. The ductility of these microenvironments are unique to different tissue types. The ECM surrounding brain, muscle and
711:
Signal induction refers to cascades of signaling events, during which a cell or tissue signals to another cell or tissue to influence its developmental fate. Yamamoto and
Jeffery investigated the role of the lens in eye formation in cave- and surface-dwelling fish, a striking example of induction.
1151:
The problem, of course, is that the candidacy of these signaling pathways was inferred primarily on the basis of their role in development and cellular differentiation. While epigenetic regulation is necessary for driving cellular differentiation, they are certainly not sufficient for this process.
1069:
During differentiation, stem cells change their gene expression profiles. Recent studies have implicated a role for nucleosome positioning and histone modifications during this process. There are two components of this process: turning off the expression of embryonic stem cell (ESC) genes, and the
981:
Alternately, upon receiving differentiation signals, PcG proteins are recruited to promoters of pluripotency transcription factors. PcG-deficient ES cells can begin differentiation but cannot maintain the differentiated phenotype. Simultaneously, differentiation and development-promoting genes are
972:
activity and resulting in transcriptional suppression. PcG knockout ES cells do not differentiate efficiently into the three germ layers, and deletion of the PRC1 and PRC2 genes leads to increased expression of lineage-affiliated genes and unscheduled differentiation. Presumably, PcG complexes are
163:
sequence itself. Metabolic composition, however, gets dramatically altered where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having
1090:
A final question to ask concerns the role of cell signaling in influencing the epigenetic processes governing differentiation. Such a role should exist, as it would be reasonable to think that extrinsic signaling can lead to epigenetic remodeling, just as it can lead to changes in gene expression
345:
and creates a single cell that has the potential to form an entire organism. In the first hours after fertilization, this cell divides into identical cells. In humans, approximately four days after fertilization and after several cycles of cell division, these cells begin to specialize, forming a
877:
However, upon examining methylation patterns more closely, the authors discovered 1175 regions of differential CG dinucleotide methylation between at least one ES or iPS cell line. By comparing these regions of differential methylation with regions of cytosine methylation in the original somatic
873:
in non-CG dinucleotides, while induced pluripotent cells possessed similar levels of methylation as embryonic stem cells, between 0.5 and 1.5%. Thus, consistent with their respective transcriptional activities, DNA methylation patterns, at least on the genomic level, are similar between ESCs and
947:
fate. Similarly, increased levels of Sox2 and decreased levels of Oct4 promote differentiation towards a neural ectodermal fate, with Sox2 inhibiting differentiation towards a mesendodermal fate. Regardless of the lineage cells differentiate down, suppression of NANOG has been identified as a
707:
pathways vary, these pathways often share the following general steps. A ligand produced by one cell binds to a receptor in the extracellular region of another cell, inducing a conformational change in the receptor. The shape of the cytoplasmic domain of the receptor changes, and the receptor
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and DNA methylation, to restrict or permit the transcription of target genes. While highly expressed, their levels require a precise balance to maintain pluripotency, perturbation of which will promote differentiation towards different lineages based on how the gene expression levels change.
1014:
of most cells of an organism is the same, the binding patterns of transcription factors and the corresponding gene expression patterns are different. To a large extent, differences in transcription factor binding are determined by the chromatin accessibility of their binding sites through
968:(PcG) family of proteins, catalyzes the di- and tri-methylation of histone H3 lysine 27 (H3K27me2/me3). By binding to the H3K27me2/3-tagged nucleosome, PRC1 (also a complex of PcG family proteins) catalyzes the mono-ubiquitinylation of histone H2A at lysine 119 (H2AK119Ub1), blocking
727:
because of an uneven distribution of regulatory molecules in the parent cell; the distinct cytoplasm that each daughter cell inherits results in a distinct pattern of differentiation for each daughter cell. A well-studied example of pattern formation by asymmetric divisions is
354:. The cells of the inner cell mass go on to form virtually all of the tissues of the human body. Although the cells of the inner cell mass can form virtually every type of cell found in the human body, they cannot form an organism. These cells are referred to as
746:, the 16 cells in the anterior hemisphere of a 32-cell embryo divide asymmetrically, each producing one large and one small daughter cell. The size of the cell at the end of all cell divisions determines whether it becomes a specialized germ or somatic cell.
334:—eggs and sperm—and thus are continuous through the generations. Stem cells, on the other hand, have the ability to divide for indefinite periods and to give rise to specialized cells. They are best described in the context of normal human development.
187:
and gut. During terminal differentiation, a precursor cell formerly capable of cell division permanently leaves the cell cycle, dismantles the cell cycle machinery and often expresses a range of genes characteristic of the cell's final function (e.g.
203:, which is the cell's ability to differentiate into other cell types. A greater potency indicates a larger number of cell types that can be derived. A cell that can differentiate into all cell types, including the placental tissue, is known as
1135:
are associated with the maintenance of mouse ESCs in an undifferentiated state. This is achieved through its activation of the Jak-STAT3 pathway, which has been shown to be necessary and sufficient towards maintaining mouse ESC pluripotency.
640:. Cell differentiation is thus a transition of a cell from one cell type to another and it involves a switch from one pattern of gene expression to another. Cellular differentiation during development can be understood as the result of a
712:
Through reciprocal transplants, Yamamoto and
Jeffery found that the lens vesicle of surface fish can induce other parts of the eye to develop in cave- and surface-dwelling fish, while the lens vesicle of the cave-dwelling fish cannot.
798:
In systems biology and mathematical modeling of gene regulatory networks, cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or
475:(listed from most distal (exterior) to proximal (interior)). The ectoderm ends up forming the skin and the nervous system, the mesoderm forms the bones and muscular tissue, and the endoderm forms the internal organ tissues.
878:
cells, 44-49% of differentially methylated regions reflected methylation patterns of the respective progenitor somatic cells, while 51-56% of these regions were dissimilar to both the progenitor and embryonic cell lines.
982:
activated by
Trithorax group (TrxG) chromatin regulators and lose their repression. TrxG proteins are recruited at regions of high transcriptional activity, where they catalyze the trimethylation of histone H3 lysine 4 (
1102:. The Wnt pathway is involved in all stages of differentiation, and the ligand Wnt3a can substitute for the overexpression of c-Myc in the generation of induced pluripotent stem cells. On the other hand, disruption of
811:
The first question that can be asked is the extent and complexity of the role of epigenetic processes in the determination of cell fate. A clear answer to this question can be seen in the 2011 paper by Lister R,
656:
gene expression, cellular differentiation is the result of a
Darwinian selective process occurring among cells. In this frame, protein and gene networks are the result of cellular processes and not their cause.
213:
are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. A cell that can differentiate into all cell types of the adult organism is known as
760:
Since each cell, regardless of cell type, possesses the same genome, determination of cell type must occur at the level of gene expression. While the regulation of gene expression can occur through
1185:
In summary, the role of signaling in the epigenetic control of cell fate in mammals is largely unknown, but distinct examples exist that indicate the likely existence of further such mechanisms.
736:
molecules are an important type of intracellular differentiation control signal. The molecular and genetic basis of asymmetric cell divisions has also been studied in green algae of the genus
1128:
proteins. Depletion of growth factors promotes the differentiation of ESCs, while genes with bivalent chromatin can become either more restrictive or permissive in their transcription.
1182:. The mechanical signal is then epigenetically transduced via signal transduction systems (of which specific molecules such as Wnt are part) to result in differential gene expression.
1401:
Yanes, Oscar; Clark, Julie; Wong, Diana M.; Patti, Gary J.; Sánchez-Ruiz, Antonio; Benton, H. Paul; Trauger, Sunia A.; Desponts, Caroline; Ding, Sheng; Siuzdak, Gary (June 2010).
1082:(nucleosome remodelling and histone deacetylase) complex, giving an instance where methylation and acetylation are not discrete and mutually exclusive, but intertwined processes.
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conserved molecular processes are involved in the cellular mechanisms underlying these switches, in animal species these are very different from the well-characterized
119:
changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a
3837:
3001:
Teif VB, Vainshtein Y, Caudron-Herger M, Mallm JP, Marth C, Höfer T, Rippe K (2012). "Genome-wide nucleosome positioning during embryonic stem cell development".
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Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ, McMahon S, Karlsson EK, Kulbokas EJ, Gingeras TR, Schreiber SL, Lander ES (Jan 2005).
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An alternative model of cellular differentiation during embryogenesis is that positional information is based on mechanical signalling by the cytoskeleton using
719:, divisions that give rise to daughter cells with distinct developmental fates. Asymmetric cell divisions can occur because of asymmetrically expressed maternal
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in their pluripotent properties, few epigenetic differences should exist between them. To test this prediction, the authors conducted whole-genome profiling of
106:
86:
66:
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in ESCs and iPSCs were methylated, the same was true of only 60% of CG dinucleotides in somatic cells. In addition, somatic cells possessed minimal levels of
644:. A regulatory gene and its cis-regulatory modules are nodes in a gene regulatory network; they receive input and create output elsewhere in the network. The
327:. Such cells, called somatic cells, make up most of the human body, such as skin and muscle cells. Cells differentiate to specialize for different functions.
889:, as seen from the similar levels of cytosine methylation between induced pluripotent and embryonic stem cells, consistent with their respective patterns of
1112:
comprise the second major set of candidates of epigenetic regulators of cellular differentiation. These morphogens are crucial for development, and include
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through the activation or repression of different transcription factors. Little direct data is available concerning the specific signals that influence the
196:
for a muscle cell). Differentiation may continue to occur after terminal differentiation if the capacity and functions of the cell undergo further changes.
2048:
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in the laboratory, cells can change shape or may lose specific properties such as protein expression—which processes are also termed dedifferentiation.
882:-induced differentiation of iPSC lines saw transmission of 88% and 46% of hyper and hypo-methylated differentially methylated regions, respectively.
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755:
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approach to developmental biology emphasizes the importance of investigating how developmental mechanisms interact to produce predictable patterns (
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Krogan NJ, Dover J, Wood A, Schneider J, Heidt J, Boateng MA, Dean K, Ryan OW, Golshani A, Johnston M, Greenblatt JF, Shilatifard A (Mar 2003).
1516:
Schöler, Hans R. (2007). "The
Potential of Stem Cells: An Inventory". In Nikolaus Knoepffler; Dagmar Schipanski; Stefan Lorenz Sorgner (eds.).
1458:
Takahashi, K; Yamanaka, S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors".
1247:
2913:"Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity"
2207:
1816:
1576:
1525:
3663:
2872:"The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation"
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DNA-nucleosome interactions are characterized by two states: either tightly bound by nucleosomes and transcriptionally inactive, called
227:
in animals, though some groups report the presence of adult pluripotent cells. Virally induced expression of four transcription factors
1628:
2841:
1603:
1148:, in addition to its role as a morphogen, promotes embryonic stem cell differentiation and the self-renewal of somatic stem cells.
699:. Many of the signal molecules that convey information from cell to cell during the control of cellular differentiation are called
3479:
Guilak, Farshid; Cohen, Daniel M.; Estes, Bradley T.; Gimble, Jeffrey M.; Liedtke, Wolfgang; Chen, Christopher S. (2009-07-02).
1951:"Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture"
2395:"Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation"
2393:
Madrigal P, Deng S, Feng Y, Militi S, Goh KJ, Nibhani R, Grandy R, Osnato A, Ortmann D, Brown S, Pauklin S (January 25, 2023).
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levels have been shown to precede germ layer fate selection. Increased levels of Oct4 and decreased levels of Sox2 promote a
820:
20:
3256:
Leung C; et al. (2004). "Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas".
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Whyte, W. A.; Bilodeau, S; Orlando, D. A.; Hoke, H. A.; Frampton, G. M.; Foster, C. T.; Cowley, S. M.; Young, R. A. (2012).
3579:
Strother, Paul K.; Brasier, Martin D.; Wacey, David; Timpe, Leslie; Saunders, Martin; Wellman, Charles H. (13 April 2021).
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1900:
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637:
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1113:
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observed significant resemblance in methylation levels between embryonic and induced pluripotent cells. Around 80% of
559:, but others explain it as a natural part of the immune response that was lost to humans at some point of evolution.
3528:
3309:"Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem cell population and proliferation"
350:. The blastocyst has an outer layer of cells, and inside this hollow sphere, there is a cluster of cells called the
1172:
1132:
574:. These manifestly dedifferentiated cells—now performing essentially as stem cells—could then redifferentiate into
483:
1862:"Evidence for dedifferentiation and metaplasia in amphibian limb regeneration from inheritance of DNA methylation"
1744:"Bidirectional radial Ca(2+) activity regulates neurogenesis and migration during early cortical column formation"
261:
are more restricted than multipotent, but can still differentiate into a few closely related cell types. Finally,
1121:
1048:
2076:
1124:(FGFs). TGFs and FGFs have been shown to sustain expression of OCT4, SOX2, and NANOG by downstream signaling to
3656:
918:– are highly expressed in undifferentiated embryonic stem cells and are necessary for the maintenance of their
890:
765:
729:
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385:
172:
307:. Each of the approximately 37.2 trillion (3.72x10) cells in an adult human has its own copy or copies of the
377:(embryonic neural stem cells) that give rise to excitatory neurons in the fetal brain through the process of
3772:
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965:
886:
685:
641:
2454:
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409:(adult stem cells) from the bone marrow that give rise to stromal cells, fat cells, and types of bone cells
1293:"Solution of the chemical master equation by radial basis functions approximation with interface tracking"
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Two conclusions are readily apparent from this study. First, epigenetic processes are heavily involved in
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3209:"Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells"
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1912:
1755:
1257:
1235:
1016:
927:
870:
824:
742:, a model system for studying how unicellular organisms can evolve into multicellular organisms. In
151:, and responsiveness to signals. These changes are largely due to highly controlled modifications in
1106:, a component of the Wnt signaling pathway, leads to decreased proliferation of neural progenitors.
910:– the first two of which are used in induced pluripotent stem cell (iPSC) reprogramming, along with
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224:
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776:, the problem arises as to how this expression pattern is maintained over numerous generations of
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2011:
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during tissue repair and during normal cell turnover. Some differentiation occurs in response to
2290:
Yamamoto, Y.; Jeffery, W. R. (2000). "Central Role for the Lens in Cave Fish Eye
Degeneration".
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processes play a crucial role in regulating the decision to adopt a stem, progenitor, or mature
48:
Cell-count distribution featuring cellular differentiation for three types of cells (progenitor
660:
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2681:"Genome-wide chromatin state transitions associated with developmental and environmental cues"
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Slack, J.M.W. (2007). "Metaplasia and transdifferentiation: from pure biology to the clinic".
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responsible for transcriptionally repressing differentiation and development-promoting genes.
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or because of signaling. In the former mechanism, distinct daughter cells are created during
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cell is one that can differentiate into multiple different, but closely related cell types.
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128:
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Kirk MM, A Ransick, SE Mcrae, DL Kirk; The relationship between cell size and cell fate in
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where a differentiated cell reverts to an earlier developmental stage—usually as part of a
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genes. Patterns of DNA methylation in ESCs, iPSCs, somatic cells were compared. Lister R,
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645:
621:
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regions of pluripotency genes, thereby inhibiting their transcription. It interacts with
3596:
3429:
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3064:
2753:
2632:"Pluripotency factors in embryonic stem cells regulate differentiation into germ layers"
2523:
2413:
2303:
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Several other signaling pathways are also considered to be primary candidates. Cytokine
994:
Regulation of gene expression is further achieved through DNA methylation, in which the
435:
A pathway that is guided by the cell adhesion molecules consisting of four amino acids,
368:
that then give rise to functional cells. Examples of stem and progenitor cells include:
159:. With a few exceptions, cellular differentiation almost never involves a change in the
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3505:
3480:
3456:
3413:
3333:
3308:
3233:
3208:
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2798:
Meissner A (2010). "Epigenetic modifications in pluripotent and differentiated cells".
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2705:
2680:
2656:
2631:
2604:
2579:
2540:
2508:"Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells"
2507:
2430:
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2024:
1991:
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1435:
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1145:
1125:
1109:
1020:
957:
696:
510:
423:
316:
176:
91:
71:
51:
3184:
3160:"Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3"
3159:
3115:
Mohammad HP, Baylin SB (2010). "Linking cell signaling and the epigenetic machinery".
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2871:
2259:
2242:
831:
patterns in several human embryonic stem cell (ESC), iPSC, and progenitor cell lines.
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2827:
2473:
1565:
1137:
845:, and foreskin fibroblasts were reprogrammed into induced pluripotent state with the
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649:
503:
428:
342:
270:
136:
27:
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3293:
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Yamamoto Y and WR Jeffery; Central role for the lens in cave fish eye degeneration.
612:
3711:
3324:
3144:
2987:
2954:"Genomic maps and comparative analysis of histone modifications in human and mouse"
2489:
2455:"Branching and oscillations in the epigenetic landscape of cell-fate determination"
1924:
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1387:
1207:
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1103:
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200:
3481:"Control of Stem Cell Fate by Physical Interactions with the Extracellular Matrix"
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522:
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Thomson, M; Liu, S. J.; Zou, L. N.; Smith, Z; Meissner, A; Ramanathan, S (2011).
2311:
1043:, or loosely bound and usually, but not always, transcriptionally active, called
1808:
1541:
1044:
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is covering a given genomic binding site or not. This can be determined using a
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842:
724:
590:
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Some hypothesize that dedifferentiation is an aberration that likely results in
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362:
355:
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1928:
1803:. Current Topics in Microbiology and Immunology. Vol. 280. pp. 1–70.
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1992:"Cellular origin of cancer: dedifferentiation or stem cell maturation arrest?"
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Slack, J.M.W. (2013) Essential
Developmental Biology. Wiley-Blackwell, Oxford.
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3049:"Enhancer decommissioning by LSD1 during embryonic stem cell differentiation"
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304:
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37:
3622:
3581:"A possible billion-year-old holozoan with differentiated multicellularity"
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2665:
2613:
2549:
2481:
2439:
2319:
2268:
2184:
2125:
2072:
1976:
1967:
1950:
1826:
1785:
1767:
1728:
1679:
1489:
1444:
1379:
1328:
3529:"Billion-year-old fossil reveals missing link in the evolution of animals"
3193:
2379:
2361:
2033:
1885:
1877:
1144:
is involved in the proliferation and self-renewal of stem cells. Finally,
3128:
2595:
1418:
1160:
879:
866:
677:
472:
468:
464:
456:
436:
398:
220:
3277:
3072:
2531:
3628:
2015:
1480:
1217:
1213:
983:
835:
684:. Specifically, cell differentiation in animals is highly dependent on
681:
633:
589:
Diagram exposing several methods used to revert adult somatic cells to
571:
440:
331:
320:
319:, that lack nuclei in their fully differentiated state. Most cells are
140:
3014:
1901:"Dedifferentiation and Regeneration in Bryophytes: A Selective Review"
1646:"Evolution of the neocortex: a perspective from developmental biology"
3734:
3724:
2811:
2064:
738:
673:
652:). However, an alternative view has been proposed recently. Based on
625:
567:
556:
448:
308:
274:
189:
165:
143:
exposure. Differentiation dramatically changes a cell's size, shape,
124:
2344:"The relationship between cell size and cell fate in Volvox carteri"
2007:
1661:
1371:
1226:
with two types of cells, shows that the evolution of differentiated
943:
fate, with Oct4 actively suppressing genes associated with a neural
418:(progenitor cells) that give rise to the various types of skin cells
265:
cells can differentiate into only one cell type, but are capable of
2202:(8th ed.). Sunderland, Mass: Sinauer Associates. p. 147.
2157:
1403:"Metabolic oxidation regulates embryonic stem cell differentiation"
44:
3729:
1267:
932:
915:
817:
659:
611:
482:
338:
237:
193:
43:
32:
1155:
Expression of Shh (Sonic hedgehog) upregulates the production of
823:. As induced pluripotent stem cells (iPSCs) are thought to mimic
1949:
Schnabel M, Marlovits S, Eckhoff G, et al. (January 2002).
1168:
1164:
1156:
1079:
1071:
961:
936:
911:
854:
850:
846:
839:
629:
537:
273:, the level of cellular differentiation is used as a measure of
242:
232:
228:
3645:
548:
process. Dedifferentiation also occurs in plant cells. And, in
1070:
activation of cell fate genes. Lysine specific demethylase 1 (
922:. It is thought that they achieve this through alterations in
858:
733:
160:
3641:
2235:
Rudel and Sommer; The evolution of developmental mechanisms.
249:) is sufficient to create pluripotent (iPS) cells from adult
3359:
Engler, AJ; Sen, S; Sweeney, HL; Discher, DE (August 2006).
2342:
Kirk, M. M.; Ransick, A.; McRae, S. E.; Kirk, D. L. (1993).
1619:
D. Binder, Marc; Hirokawa, Nobutaka; Windhorst, Uwe (2009).
295:
Three basic categories of cells make up the mammalian body:
19:"Cell differentiation" redirects here. For the journal, see
3554:"Billion-year-old fossil found preserved in Torridon rocks"
3361:"Matrix Elasticity Directs Stem Cell Lineage Specification"
1860:
Casimir CM, Gates PB, Patient RK, Brockes JP (1988-12-01).
1799:
361:
Pluripotent stem cells undergo further specialization into
281:" is a marker of how differentiated a cell in a tumor is.
131:
and cell types. Differentiation continues in adulthood as
2141:"Cell differentiation: what have we learned in 50 years?"
636:. Each cell type is defined by its particular pattern of
532:, or integration, is a cellular process seen in the more
175:, is of importance in some tissues, including vertebrate
1140:
can induce differentiation of human and mouse ESCs, and
330:
Germ line cells are any line of cells that give rise to
16:
Transformation of a stem cell to a more specialized cell
1571:(4th ed.). New York: W. H. Freeman. Section 14.2.
2099:"Gene regulation: gene control network in development"
715:
Other important mechanisms fall under the category of
1273:
List of human cell types derived from the germ layers
427:(progenitor cells) that contribute to differentiated
94:
74:
54:
3805:
3710:
3679:
1693:Lui, JH; Hansen, DV; Kriegstein, AR (8 July 2011).
1598:. I.K. International Publishing House. p. 22.
1230:, possibly but not necessarily of animal lineages,
1023:. In particular, it is important to know whether a
513:, showing a few blood vessels, (center of image). (
291:
List of distinct cell types in the adult human body
199:Among dividing cells, there are multiple levels of
1695:"Development and evolution of the human neocortex"
1564:
664:An overview of major signal transduction pathways.
570:analog, has proven to induce dedifferentiation in
100:
80:
60:
2573:
2571:
2569:
2567:
2565:
2563:
2561:
2559:
1159:, a component of the PcG complex that recognizes
2911:Ng HH, Robert F, Young RA, Struhl K (Mar 2003).
2580:"Epigenetic control of embryonic stem cell fate"
1742:Rash, BG; Ackman, JB; Rakic, P (February 2016).
695:Cellular differentiation is often controlled by
171:A specialized type of differentiation, known as
40:differentiation into various animal tissue types
3418:Proceedings of the National Academy of Sciences
3838:Stem cell laws and policy in the United States
3158:Niwa H, Burdon T, Chambers I, Smith A (1998).
2453:Rabajante JF, Babierra AL (January 30, 2015).
1291:Kryven, I.; Röblitz, S.; Schütte, Ch. (2015).
680:, and even from those of the animals' closest
3657:
3042:
3040:
2625:
2623:
906:Three transcription factors, OCT4, SOX2, and
209:. In mammals, only the zygote and subsequent
8:
2462:Progress in Biophysics and Molecular Biology
1163:. This occurs in a Gli-dependent manner, as
948:necessary prerequisite for differentiation.
3110:
3108:
3106:
3104:
3102:
3100:
2793:
2791:
2789:
2728:
2726:
2724:
2280:
2278:
2243:"The evolution of developmental mechanisms"
3664:
3650:
3642:
2198:Knisely, Karen; Gilbert, Scott F. (2009).
1511:
1509:
1507:
620:Each specialized cell type in an organism
3604:
3504:
3455:
3437:
3376:
3332:
3232:
3183:
3080:
2969:
2928:
2887:
2769:
2704:
2655:
2603:
2539:
2501:
2499:
2429:
2369:
2258:
2174:
2156:
2097:Ben-Tabou de-Leon S, Davidson EH (2007).
2023:
1966:
1775:
1718:
1669:
1479:
1434:
1318:
1308:
93:
73:
53:
3843:Epigenetics in stem cell differentiation
2231:
2229:
2227:
2225:
2223:
2221:
2219:
2118:10.1146/annurev.biophys.35.040405.102002
756:Epigenetics in stem cell differentiation
584:
451:, is created as the cellular blastomere
1283:
1086:Role of signaling in epigenetic control
135:divide and create fully differentiated
2049:"Stem cells from differentiated cells"
1842:
1832:
1518:Humanbiotechnology as Social Challenge
1248:Interbilayer Forces in Membrane Fusion
816:on aberrant epigenomic programming in
616:Mechanisms of cellular differentiation
3354:
3352:
1360:Nature Reviews Molecular Cell Biology
1232:occurred at least 1 billion years ago
788:This section will focus primarily on
108:) exposed to pro-osteoblast stimulus.
7:
3414:"Actin stress in cell reprogramming"
2578:Christophersen NS, Helin K (2010).
1801:Regeneration: Stem Cells and Beyond
1074:) is thought to prevent the use of
1035:Histone acetylation and methylation
902:Pioneer factors (Oct4, Sox2, Nanog)
897:Mechanisms of epigenetic regulation
703:. Although the details of specific
632:that constitute the genome of that
562:A newly discovered molecule dubbed
393:that give rise to red blood cells,
1520:. Ashgate Publishing. p. 28.
952:Polycomb repressive complex (PRC2)
730:body axis patterning in Drosophila
14:
2241:Rudel, D.; Sommer, R. J. (2003).
346:hollow sphere of cells, called a
3856:
3855:
3627:
2474:10.1016/j.pbiomolbio.2015.01.006
1542:"NCI Dictionary of Cancer Terms"
1334:
1171:are downstream effectors of the
807:Importance of epigenetic control
1180:Embryonic differentiation waves
1002:upon in vitro differentiation.
977:Trithorax group proteins (TrxG)
608:Embryonic differentiation waves
536:life forms in animals, such as
494:, (at left edge of image). + A
323:; they have two copies of each
3702:Induced pluripotent stem cells
3325:10.1523/JNEUROSCI.3452-04.2005
3307:Zencak D; et al. (2005).
2733:Guenther MG, Young RA (2010).
2506:Lister R; et al. (2011).
2145:Journal of Theoretical Biology
2106:Annu Rev Biophys Biomol Struct
1925:10.1080/0028825x.1971.10430231
821:induced pluripotent stem cells
21:Cell Differentiation (journal)
1:
3412:; Meng, Fanjie (2014-12-09).
3225:10.1158/0008-5472.CAN-06-0054
2930:10.1016/S1097-2765(03)00092-3
2889:10.1016/S1097-2765(03)00091-1
2842:"Chromatin Immuprecipitation"
2679:Zhu, J.; et al. (2013).
2260:10.1016/S0012-1606(03)00353-1
1905:New Zealand Journal of Botany
1098:The first major candidate is
1029:chromatin immunoprecipitation
962:Polycomb repressive complex 2
2312:10.1126/science.289.5479.631
1650:Nature Reviews. Neuroscience
1621:Encyclopedia of Neuroscience
1595:Textbook of Human Embryology
1212:A billion-years-old, likely
964:, one of two classes of the
389:(adult stem cells) from the
123:as it changes from a simple
3207:Liu S; et al. (2006).
1809:10.1007/978-3-642-18846-6_1
1544:. National Cancer Institute
1189:Effect of matrix elasticity
1133:leukemia inhibitory factors
1118:transforming growth factors
1114:bone morphogenetic proteins
931:Differential regulation of
688:of regulatory proteins and
506:, (right edge of image). +
3912:
3497:10.1016/j.stem.2009.06.016
3378:10.1016/j.cell.2006.06.044
2971:10.1016/j.cell.2005.01.001
2735:"Repressive Transcription"
2697:10.1016/j.cell.2012.12.033
2648:10.1016/j.cell.2011.05.017
2422:10.1038/s41467-023-36116-9
2288:289 (5479), 631-633, 2000
2176:10.1016/j.jtbi.2019.110031
2139:Newman, Stuart A. (2020).
1711:10.1016/j.cell.2011.06.030
1472:10.1016/j.cell.2006.07.024
1205:
1173:Hedgehog signaling pathway
1062:
1049:histone acetyltransferases
753:
674:gene regulatory mechanisms
605:
337:Development begins when a
288:
115:is the process in which a
25:
18:
3851:
3606:10.1016/j.cub.2021.03.051
1644:Rakic, P (October 2009).
1310:10.1186/s12918-015-0210-y
1122:fibroblast growth factors
766:trans-regulatory elements
717:asymmetric cell divisions
638:regulated gene expression
3813:Cellular differentiation
3408:Guo, Jun; Wang, Yuexiu;
2047:Tsonis PA (April 2004).
1996:Environ. Health Perspect
1990:Sell S (December 1993).
721:cytoplasmic determinants
686:biomolecular condensates
455:from the single-layered
386:Hematopoietic stem cells
219:. Such cells are called
173:terminal differentiation
113:Cellular differentiation
26:Not to be confused with
3773:Hematopoietic stem cell
3439:10.1073/pnas.1411683111
2762:10.1126/science.1193995
2349:Journal of Cell Biology
2338:Journal of Cell Biology
1563:Lodish, Harvey (2000).
1407:Nature Chemical Biology
1238:rather than the ocean.
1234:and possibly mainly in
887:cell fate determination
642:gene regulatory network
463:in mammals, namely the
127:to a complex system of
3176:10.1101/gad.12.13.2048
1968:10.1053/joca.2001.0482
1768:10.1126/sciadv.1501733
1567:Molecular Cell Biology
1006:Nucleosome positioning
665:
617:
598:
526:
492:some dedifferentiation
406:Mesenchymal stem cells
121:multicellular organism
109:
102:
82:
62:
41:
3889:Developmental biology
3823:Stem cell controversy
3778:Mesenchymal stem cell
3768:Endothelial stem cell
2402:Nature Communications
2362:10.1083/jcb.123.1.191
2247:Developmental Biology
2237:Developmental Biology
2200:Developmental Biology
1878:10.1242/dev.104.4.657
1100:Wnt signaling pathway
1063:Further information:
996:DNA methyltransferase
682:unicellular relatives
663:
615:
588:
486:
459:to the three primary
223:in higher plants and
155:and are the study of
103:
83:
63:
47:
36:
3687:Embryonic stem cells
3591:(12): 2658–2665.e2.
3129:10.1038/nbt1010-1033
2846:www.bio.brandeis.edu
2596:10.1084/jem.20101438
1592:Kumar, Rani (2008).
1419:10.1038/nchembio.364
1258:Lipid bilayer fusion
1202:Evolutionary history
1017:histone modification
928:histone modification
871:cytosine methylation
825:embryonic stem cells
508:Fully differentiated
461:layers of germ cells
285:Mammalian cell types
225:embryonic stem cells
92:
72:
52:
3747:Embryonic stem cell
3597:2021CBio...31E2658S
3430:2014PNAS..111E5252G
3424:(49): E5252–E5261.
3278:10.1038/nature02385
3270:2004Natur.428..337L
3073:10.1038/nature10805
3065:2012Natur.482..221W
3003:Nat Struct Mol Biol
2754:2010Sci...329..150G
2532:10.1038/nature09798
2524:2011Natur.471...68L
2414:2023NatCo..14..405M
2340:123, 191-208, 1993
2304:2000Sci...289..631Y
2167:2020JThBi.48510031N
1917:1971NZJB....9..689G
1760:2016SciA....2E1733R
1297:BMC Systems Biology
1053:histone deactylases
926:structure, such as
780:. As it turns out,
768:including a gene's
705:signal transduction
498:component, showing
3894:Induced stem cells
3884:Cellular processes
2002:(Suppl 5): 15–26.
1955:Osteoarthr. Cartil
1263:Cell-cell fusogens
803:) or oscillatory.
750:Epigenetic control
666:
618:
599:
527:
374:Radial glial cells
221:meristematic cells
149:metabolic activity
145:membrane potential
110:
98:
88:, and chondrocyte
78:
58:
42:
3871:
3870:
3818:Stem cell therapy
3697:Cancer stem cells
3015:10.1038/nsmb.2419
2298:(5479): 631–633.
2239:264, 15-37, 2003
2209:978-0-87893-371-6
1899:Giles KL (1971).
1818:978-3-540-02238-1
1578:978-0-7167-3136-8
1527:978-0-7546-5755-2
1223:Bicellum brasieri
1080:Mi-2/NuRD complex
970:RNA polymerase II
801:strange attractor
530:Dedifferentiation
479:Dedifferentiation
395:white blood cells
259:Oligopotent cells
101:{\displaystyle x}
81:{\displaystyle y}
61:{\displaystyle z}
3901:
3859:
3858:
3806:Related articles
3783:Neural stem cell
3692:Adult stem cells
3666:
3659:
3652:
3643:
3637:
3632:Available under
3631:
3626:
3608:
3576:
3570:
3569:
3567:
3565:
3550:
3544:
3543:
3541:
3539:
3525:
3519:
3518:
3508:
3476:
3470:
3469:
3459:
3441:
3410:Sachs, Frederick
3405:
3399:
3398:
3380:
3356:
3347:
3346:
3336:
3304:
3298:
3297:
3264:(6980): 337–41.
3253:
3247:
3246:
3236:
3204:
3198:
3197:
3187:
3155:
3149:
3148:
3112:
3095:
3094:
3084:
3044:
3035:
3034:
2998:
2992:
2991:
2973:
2949:
2943:
2942:
2932:
2908:
2902:
2901:
2891:
2867:
2861:
2860:
2858:
2857:
2848:. Archived from
2838:
2832:
2831:
2812:10.1038/nbt.1684
2795:
2784:
2783:
2773:
2739:
2730:
2719:
2718:
2708:
2676:
2670:
2669:
2659:
2627:
2618:
2617:
2607:
2575:
2554:
2553:
2543:
2503:
2494:
2493:
2459:
2450:
2444:
2443:
2433:
2399:
2390:
2384:
2383:
2373:
2330:
2324:
2323:
2282:
2273:
2272:
2262:
2233:
2214:
2213:
2195:
2189:
2188:
2178:
2160:
2136:
2130:
2129:
2112:(191): 191–212.
2103:
2094:
2088:
2087:
2085:
2084:
2075:. Archived from
2065:10.1124/mi.4.2.4
2044:
2038:
2037:
2027:
1987:
1981:
1980:
1970:
1946:
1940:
1939:
1937:
1936:
1927:. Archived from
1896:
1890:
1889:
1857:
1851:
1850:
1844:
1840:
1838:
1830:
1796:
1790:
1789:
1779:
1748:Science Advances
1739:
1733:
1732:
1722:
1690:
1684:
1683:
1673:
1641:
1635:
1634:
1616:
1610:
1609:
1589:
1583:
1582:
1570:
1560:
1554:
1553:
1551:
1549:
1538:
1532:
1531:
1513:
1502:
1501:
1483:
1455:
1449:
1448:
1438:
1398:
1392:
1391:
1355:
1349:
1346:
1340:
1339:
1338:
1332:
1322:
1312:
1288:
1253:Fusion mechanism
1236:freshwater lakes
1228:multicellularity
956:In the realm of
867:CG dinucleotides
366:progenitor cells
247:Yamanaka factors
240:
133:adult stem cells
107:
105:
104:
99:
87:
85:
84:
79:
67:
65:
64:
59:
3911:
3910:
3904:
3903:
3902:
3900:
3899:
3898:
3874:
3873:
3872:
3867:
3847:
3801:
3764:Progenitor cell
3706:
3675:
3670:
3640:
3585:Current Biology
3578:
3577:
3573:
3563:
3561:
3552:
3551:
3547:
3537:
3535:
3527:
3526:
3522:
3478:
3477:
3473:
3407:
3406:
3402:
3358:
3357:
3350:
3319:(24): 5774–83.
3306:
3305:
3301:
3255:
3254:
3250:
3219:(12): 6063–71.
3206:
3205:
3201:
3170:(13): 2048–60.
3157:
3156:
3152:
3114:
3113:
3098:
3059:(7384): 221–5.
3046:
3045:
3038:
3009:(11): 1185–92.
3000:
2999:
2995:
2951:
2950:
2946:
2910:
2909:
2905:
2869:
2868:
2864:
2855:
2853:
2840:
2839:
2835:
2806:(10): 1079–88.
2797:
2796:
2787:
2748:(5988): 150–1.
2737:
2732:
2731:
2722:
2678:
2677:
2673:
2629:
2628:
2621:
2590:(11): 2287–95.
2577:
2576:
2557:
2518:(7336): 68–73.
2505:
2504:
2497:
2457:
2452:
2451:
2447:
2397:
2392:
2391:
2387:
2341:
2331:
2327:
2289:
2283:
2276:
2240:
2234:
2217:
2210:
2197:
2196:
2192:
2138:
2137:
2133:
2101:
2096:
2095:
2091:
2082:
2080:
2046:
2045:
2041:
2008:10.2307/3431838
1989:
1988:
1984:
1948:
1947:
1943:
1934:
1932:
1898:
1897:
1893:
1859:
1858:
1854:
1841:
1831:
1819:
1798:
1797:
1793:
1754:(2): e1501733.
1741:
1740:
1736:
1692:
1691:
1687:
1662:10.1038/nrn2719
1643:
1642:
1638:
1631:
1618:
1617:
1613:
1606:
1591:
1590:
1586:
1579:
1562:
1561:
1557:
1547:
1545:
1540:
1539:
1535:
1528:
1515:
1514:
1505:
1457:
1456:
1452:
1400:
1399:
1395:
1372:10.1038/nrm2146
1357:
1356:
1352:
1347:
1343:
1333:
1290:
1289:
1285:
1281:
1244:
1210:
1204:
1191:
1142:Notch signaling
1088:
1067:
1061:
1041:heterochromatin
1037:
1021:pioneer factors
1008:
992:
990:DNA methylation
979:
954:
904:
899:
829:DNA methylation
809:
758:
752:
692:DNA sequences.
646:systems biology
610:
604:
481:
424:satellite cells
352:inner cell mass
317:red blood cells
311:except certain
293:
287:
236:
181:striated muscle
153:gene expression
90:
89:
70:
69:
50:
49:
31:
24:
17:
12:
11:
5:
3909:
3908:
3905:
3897:
3896:
3891:
3886:
3876:
3875:
3869:
3868:
3866:
3865:
3852:
3849:
3848:
3846:
3845:
3840:
3835:
3833:Stem cell laws
3830:
3828:Stem cell line
3825:
3820:
3815:
3809:
3807:
3803:
3802:
3800:
3799:
3798:
3797:
3795:Precursor cell
3787:
3786:
3785:
3780:
3775:
3770:
3756:
3755:
3754:
3749:
3739:
3738:
3737:
3732:
3727:
3716:
3714:
3708:
3707:
3705:
3704:
3699:
3694:
3689:
3683:
3681:
3677:
3676:
3671:
3669:
3668:
3661:
3654:
3646:
3639:
3638:
3571:
3545:
3520:
3485:Cell Stem Cell
3471:
3400:
3371:(4): 677–689.
3348:
3299:
3248:
3199:
3150:
3123:(10): 1033–8.
3117:Nat Biotechnol
3096:
3036:
2993:
2944:
2917:Molecular Cell
2903:
2876:Molecular Cell
2862:
2833:
2800:Nat Biotechnol
2785:
2720:
2691:(3): 642–654.
2671:
2619:
2555:
2495:
2468:(2–3): 240–9.
2445:
2385:
2356:(1): 191–208.
2334:Volvox carteri
2325:
2274:
2215:
2208:
2190:
2131:
2089:
2039:
1982:
1941:
1891:
1872:(4): 657–668.
1852:
1843:|journal=
1817:
1791:
1734:
1685:
1656:(10): 724–35.
1636:
1630:978-3540237358
1629:
1611:
1604:
1584:
1577:
1555:
1533:
1526:
1503:
1450:
1413:(6): 411–417.
1393:
1366:(5): 369–378.
1350:
1341:
1282:
1280:
1277:
1276:
1275:
1270:
1265:
1260:
1255:
1250:
1243:
1240:
1203:
1200:
1190:
1187:
1146:Sonic hedgehog
1110:Growth factors
1087:
1084:
1060:
1057:
1036:
1033:
1007:
1004:
991:
988:
978:
975:
966:Polycomb group
958:gene silencing
953:
950:
903:
900:
898:
895:
808:
805:
754:Main article:
751:
748:
744:Volvox carteri
701:growth factors
697:cell signaling
670:evolutionarily
603:
600:
521:prepared with
511:adipose tissue
502:and increased
496:differentiated
480:
477:
453:differentiates
433:
432:
419:
410:
402:
382:
341:fertilizes an
286:
283:
277:progression. "
177:nervous system
137:daughter cells
97:
77:
57:
15:
13:
10:
9:
6:
4:
3:
2:
3907:
3906:
3895:
3892:
3890:
3887:
3885:
3882:
3881:
3879:
3864:
3863:
3854:
3853:
3850:
3844:
3841:
3839:
3836:
3834:
3831:
3829:
3826:
3824:
3821:
3819:
3816:
3814:
3811:
3810:
3808:
3804:
3796:
3793:
3792:
3791:
3788:
3784:
3781:
3779:
3776:
3774:
3771:
3769:
3765:
3762:
3761:
3760:
3757:
3753:
3750:
3748:
3745:
3744:
3743:
3740:
3736:
3733:
3731:
3728:
3726:
3723:
3722:
3721:
3718:
3717:
3715:
3713:
3709:
3703:
3700:
3698:
3695:
3693:
3690:
3688:
3685:
3684:
3682:
3680:Sources/types
3678:
3674:
3667:
3662:
3660:
3655:
3653:
3648:
3647:
3644:
3635:
3630:
3624:
3620:
3616:
3612:
3607:
3602:
3598:
3594:
3590:
3586:
3582:
3575:
3572:
3559:
3555:
3549:
3546:
3534:
3530:
3524:
3521:
3516:
3512:
3507:
3502:
3498:
3494:
3490:
3486:
3482:
3475:
3472:
3467:
3463:
3458:
3453:
3449:
3445:
3440:
3435:
3431:
3427:
3423:
3419:
3415:
3411:
3404:
3401:
3396:
3392:
3388:
3384:
3379:
3374:
3370:
3366:
3362:
3355:
3353:
3349:
3344:
3340:
3335:
3330:
3326:
3322:
3318:
3314:
3310:
3303:
3300:
3295:
3291:
3287:
3283:
3279:
3275:
3271:
3267:
3263:
3259:
3252:
3249:
3244:
3240:
3235:
3230:
3226:
3222:
3218:
3214:
3210:
3203:
3200:
3195:
3191:
3186:
3181:
3177:
3173:
3169:
3165:
3161:
3154:
3151:
3146:
3142:
3138:
3134:
3130:
3126:
3122:
3118:
3111:
3109:
3107:
3105:
3103:
3101:
3097:
3092:
3088:
3083:
3078:
3074:
3070:
3066:
3062:
3058:
3054:
3050:
3043:
3041:
3037:
3032:
3028:
3024:
3020:
3016:
3012:
3008:
3004:
2997:
2994:
2989:
2985:
2981:
2977:
2972:
2967:
2964:(2): 169–81.
2963:
2959:
2955:
2948:
2945:
2940:
2936:
2931:
2926:
2923:(3): 709–19.
2922:
2918:
2914:
2907:
2904:
2899:
2895:
2890:
2885:
2881:
2877:
2873:
2866:
2863:
2852:on 2017-11-25
2851:
2847:
2843:
2837:
2834:
2829:
2825:
2821:
2817:
2813:
2809:
2805:
2801:
2794:
2792:
2790:
2786:
2781:
2777:
2772:
2767:
2763:
2759:
2755:
2751:
2747:
2743:
2736:
2729:
2727:
2725:
2721:
2716:
2712:
2707:
2702:
2698:
2694:
2690:
2686:
2682:
2675:
2672:
2667:
2663:
2658:
2653:
2649:
2645:
2642:(6): 875–89.
2641:
2637:
2633:
2626:
2624:
2620:
2615:
2611:
2606:
2601:
2597:
2593:
2589:
2585:
2581:
2574:
2572:
2570:
2568:
2566:
2564:
2562:
2560:
2556:
2551:
2547:
2542:
2537:
2533:
2529:
2525:
2521:
2517:
2513:
2509:
2502:
2500:
2496:
2491:
2487:
2483:
2479:
2475:
2471:
2467:
2463:
2456:
2449:
2446:
2441:
2437:
2432:
2427:
2423:
2419:
2415:
2411:
2407:
2403:
2396:
2389:
2386:
2381:
2377:
2372:
2367:
2363:
2359:
2355:
2351:
2350:
2345:
2339:
2335:
2329:
2326:
2321:
2317:
2313:
2309:
2305:
2301:
2297:
2293:
2287:
2281:
2279:
2275:
2270:
2266:
2261:
2256:
2252:
2248:
2244:
2238:
2232:
2230:
2228:
2226:
2224:
2222:
2220:
2216:
2211:
2205:
2201:
2194:
2191:
2186:
2182:
2177:
2172:
2168:
2164:
2159:
2154:
2150:
2146:
2142:
2135:
2132:
2127:
2123:
2119:
2115:
2111:
2107:
2100:
2093:
2090:
2079:on 2016-05-23
2078:
2074:
2070:
2066:
2062:
2058:
2054:
2050:
2043:
2040:
2035:
2031:
2026:
2021:
2017:
2013:
2009:
2005:
2001:
1997:
1993:
1986:
1983:
1978:
1974:
1969:
1964:
1960:
1956:
1952:
1945:
1942:
1931:on 2008-12-04
1930:
1926:
1922:
1918:
1914:
1911:(4): 689–94.
1910:
1906:
1902:
1895:
1892:
1887:
1883:
1879:
1875:
1871:
1867:
1863:
1856:
1853:
1848:
1836:
1828:
1824:
1820:
1814:
1810:
1806:
1802:
1795:
1792:
1787:
1783:
1778:
1773:
1769:
1765:
1761:
1757:
1753:
1749:
1745:
1738:
1735:
1730:
1726:
1721:
1716:
1712:
1708:
1704:
1700:
1696:
1689:
1686:
1681:
1677:
1672:
1667:
1663:
1659:
1655:
1651:
1647:
1640:
1637:
1632:
1626:
1622:
1615:
1612:
1607:
1605:9788190675710
1601:
1597:
1596:
1588:
1585:
1580:
1574:
1569:
1568:
1559:
1556:
1543:
1537:
1534:
1529:
1523:
1519:
1512:
1510:
1508:
1504:
1499:
1495:
1491:
1487:
1482:
1477:
1473:
1469:
1466:(4): 663–76.
1465:
1461:
1454:
1451:
1446:
1442:
1437:
1432:
1428:
1424:
1420:
1416:
1412:
1408:
1404:
1397:
1394:
1389:
1385:
1381:
1377:
1373:
1369:
1365:
1361:
1354:
1351:
1345:
1342:
1337:
1330:
1326:
1321:
1316:
1311:
1306:
1302:
1298:
1294:
1287:
1284:
1278:
1274:
1271:
1269:
1266:
1264:
1261:
1259:
1256:
1254:
1251:
1249:
1246:
1245:
1241:
1239:
1237:
1233:
1229:
1225:
1224:
1219:
1215:
1209:
1201:
1199:
1197:
1188:
1186:
1183:
1181:
1176:
1174:
1170:
1166:
1162:
1158:
1153:
1149:
1147:
1143:
1139:
1138:Retinoic acid
1134:
1129:
1127:
1123:
1119:
1115:
1111:
1107:
1105:
1101:
1096:
1094:
1085:
1083:
1081:
1077:
1073:
1066:
1059:In stem cells
1058:
1056:
1054:
1050:
1046:
1042:
1034:
1032:
1030:
1026:
1022:
1018:
1013:
1005:
1003:
1001:
997:
989:
987:
985:
976:
974:
971:
967:
963:
959:
951:
949:
946:
942:
941:mesendodermal
938:
934:
929:
925:
921:
917:
913:
909:
901:
896:
894:
892:
891:transcription
888:
883:
881:
875:
872:
868:
864:
860:
856:
852:
848:
844:
841:
837:
832:
830:
826:
822:
819:
815:
806:
804:
802:
796:
794:
791:
787:
783:
779:
778:cell division
775:
771:
767:
763:
757:
749:
747:
745:
741:
740:
735:
731:
726:
722:
718:
713:
709:
706:
702:
698:
693:
691:
687:
683:
679:
675:
671:
662:
658:
655:
651:
650:morphogenesis
647:
643:
639:
635:
631:
627:
623:
614:
609:
601:
596:
592:
587:
583:
581:
577:
573:
569:
565:
560:
558:
553:
551:
547:
543:
539:
535:
531:
524:
523:H&E stain
520:
516:
512:
509:
505:
501:
497:
493:
489:
485:
478:
476:
474:
470:
466:
462:
458:
454:
450:
446:
442:
438:
430:
429:muscle tissue
426:
425:
420:
417:
415:
411:
408:
407:
403:
400:
396:
392:
388:
387:
383:
380:
376:
375:
371:
370:
369:
367:
364:
359:
357:
353:
349:
344:
340:
335:
333:
328:
326:
322:
318:
314:
310:
306:
302:
301:somatic cells
298:
292:
284:
282:
280:
276:
272:
271:cytopathology
268:
264:
260:
256:
252:
248:
244:
239:
234:
230:
226:
222:
218:
217:
212:
208:
207:
202:
197:
195:
191:
186:
182:
178:
174:
169:
167:
162:
158:
154:
150:
146:
142:
138:
134:
130:
126:
122:
118:
114:
95:
75:
68:, osteoblast
55:
46:
39:
35:
29:
28:Cell division
22:
3860:
3812:
3789:
3758:
3741:
3719:
3712:Cell potency
3588:
3584:
3574:
3562:. Retrieved
3560:. 2021-04-29
3557:
3548:
3536:. Retrieved
3532:
3523:
3491:(1): 17–26.
3488:
3484:
3474:
3421:
3417:
3403:
3368:
3364:
3316:
3312:
3302:
3261:
3257:
3251:
3216:
3212:
3202:
3167:
3163:
3153:
3120:
3116:
3056:
3052:
3006:
3002:
2996:
2961:
2957:
2947:
2920:
2916:
2906:
2882:(3): 721–9.
2879:
2875:
2865:
2854:. Retrieved
2850:the original
2845:
2836:
2803:
2799:
2745:
2741:
2688:
2684:
2674:
2639:
2635:
2587:
2583:
2515:
2511:
2465:
2461:
2448:
2408:(405): 405.
2405:
2401:
2388:
2353:
2347:
2337:
2333:
2328:
2295:
2291:
2285:
2253:(1): 15–37.
2250:
2246:
2236:
2199:
2193:
2148:
2144:
2134:
2109:
2105:
2092:
2081:. Retrieved
2077:the original
2056:
2052:
2042:
1999:
1995:
1985:
1961:(1): 62–70.
1958:
1954:
1944:
1933:. Retrieved
1929:the original
1908:
1904:
1894:
1869:
1865:
1855:
1800:
1794:
1751:
1747:
1737:
1705:(1): 18–36.
1702:
1698:
1688:
1653:
1649:
1639:
1623:. Springer.
1620:
1614:
1594:
1587:
1566:
1558:
1546:. Retrieved
1536:
1517:
1463:
1459:
1453:
1410:
1406:
1396:
1363:
1359:
1353:
1344:
1300:
1296:
1286:
1221:
1211:
1208:Bangiomorpha
1196:blebbistatin
1192:
1184:
1177:
1154:
1150:
1130:
1120:(TGFs), and
1108:
1097:
1089:
1068:
1038:
1012:DNA sequence
1009:
993:
980:
955:
920:pluripotency
905:
884:
876:
862:
833:
813:
810:
797:
759:
743:
737:
720:
714:
710:
694:
667:
619:
595:pluripotency
561:
554:
550:cell culture
546:regenerative
528:
507:
495:
491:
434:
421:
412:
404:
384:
379:neurogenesis
372:
360:
336:
329:
294:
267:self-renewal
214:
204:
201:cell potency
198:
170:
112:
111:
3759:Multipotent
3742:Pluripotent
2059:(2): 81–3.
2053:Mol. Interv
1866:Development
1481:2433/159777
1045:euchromatin
843:fibroblasts
725:cytokinesis
628:of all the
591:totipotency
576:osteoblasts
519:liposarcoma
504:vascularity
391:bone marrow
363:multipotent
356:pluripotent
255:multipotent
251:fibroblasts
216:pluripotent
211:blastomeres
157:epigenetics
3878:Categories
3720:Totipotent
3673:Stem cells
3313:J Neurosci
3213:Cancer Res
2856:2016-12-26
2158:1907.09551
2151:: 110031.
2083:2010-12-26
1935:2008-01-01
1548:1 November
1279:References
1206:See also:
1025:nucleosome
1010:While the
945:ectodermal
793:stem cells
782:epigenetic
654:stochastic
606:See also:
602:Mechanisms
580:adipocytes
542:amphibians
515:Micrograph
500:lipoblasts
488:Micrograph
445:asparagine
416:stem cells
414:Epithelial
348:blastocyst
325:chromosome
315:, such as
313:cell types
305:stem cells
297:germ cells
289:See also:
206:totipotent
3790:Unipotent
3634:CC BY 4.0
3615:0960-9822
3448:0027-8424
3164:Genes Dev
2828:205274850
2584:J Exp Med
1845:ignored (
1835:cite book
1427:1552-4469
1303:(1): 67.
1104:β-catenin
1093:epigenome
1065:Stem cell
1000:apoptosis
924:chromatin
790:mammalian
786:cell fate
774:enhancers
622:expresses
564:reversine
399:platelets
263:unipotent
185:epidermis
164:the same
117:stem cell
38:Stem cell
3862:Category
3623:33852871
3558:BBC News
3533:phys.org
3515:19570510
3466:25422450
3395:16109483
3387:16923388
3343:15958744
3294:29965488
3286:15029199
3243:16778178
3137:20944593
3091:22297846
3031:34509771
3023:23085715
2980:15680324
2939:12667453
2898:12667454
2820:20944600
2780:20616255
2715:23333102
2666:21663792
2614:20975044
2550:21289626
2482:25641423
2440:36697417
2320:10915628
2286:Science
2269:14623229
2185:31568790
2126:17291181
2073:15087480
1977:11795984
1827:14594207
1786:26933693
1729:21729779
1680:19763105
1490:16904174
1445:20436487
1380:17377526
1329:26449665
1242:See also
1214:holozoan
1161:H3K27me3
1076:enhancer
880:In vitro
770:promoter
690:enhancer
678:bacteria
572:myotubes
490:showing
473:endoderm
469:mesoderm
465:ectoderm
457:blastula
437:arginine
3593:Bibcode
3506:2768283
3457:4267376
3426:Bibcode
3334:6724881
3266:Bibcode
3234:4386278
3194:9649508
3145:6911946
3082:4144424
3061:Bibcode
2988:7193829
2771:3006433
2750:Bibcode
2742:Science
2706:3563935
2657:5603300
2605:2964577
2541:3100360
2520:Bibcode
2490:2579314
2431:9876972
2410:Bibcode
2380:8408198
2371:2119814
2300:Bibcode
2292:Science
2163:Bibcode
2034:7516873
2025:1519468
2016:3431838
1913:Bibcode
1886:3268408
1777:4771444
1756:Bibcode
1720:3610574
1671:2913577
1498:1565219
1436:2873061
1388:3353748
1320:4599742
1218:protist
1031:assay.
1019:and/or
984:H3K4me3
874:iPSCs.
838:cells,
836:adipose
834:Female
634:species
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