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Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage

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Torres-Padilla, Maria-Elena, Chambers, Ian·2014·Development
DOI 10.1242/dev.102624
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Abstract

When pluripotent cells are exposed to a uniform culture environment they routinely display heterogeneous gene expression. Aspects of this heterogeneity, such as Nanog expression, are linked to differences in the propensity of individual cells to either self-renew or commit towards differentiation. Recent findings have provided new insight into the underlying causes of this heterogeneity, which we summarise here using Nanog, a key regulator of pluripotency, as a model gene. We discuss the role of transcription factor heterogeneity in facilitating the intrinsically dynamic and stochastic nature of the pluripotency network, which in turn provides a potential benefit to a population of cells that needs to balance cell fate decisions.

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Research works printed but not linked: 81

  1. Abranches, 2013, Generation and characterization of a novel mouse embryonic stem cell line with a dynamic reporter of Nanog expression, PLoS ONE, 8, e59928, 10.1371/journal.pone.0059928 · DOI
  2. Ambrosetti, 1997, Synergistic activation of the fibroblast growth factor 4 enhancer by sox2 and oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites, Mol. Cell. Biol., 17, 6321, 10.1128/MCB.17.11.6321 · DOI · Paper page
  3. Beddington, 1983, Histogenetic and neoplastic potential of different regions of the mouse embryonic egg cylinder, J. Embryol. Exp. Morphol., 75, 189
  4. Brons, 2007, Derivation of pluripotent epiblast stem cells from mammalian embryos, Nature, 448, 191, 10.1038/nature05950 · DOI · Paper page
  5. Brook, 1997, The origin and efficient derivation of embryonic stem cells in the mouse, Proc. Natl. Acad. Sci. U.S.A., 94, 5709, 10.1073/pnas.94.11.5709 · DOI · Paper page
  6. Brookes, 2009, Modifications of RNA polymerase II are pivotal in regulating gene expression states, EMBO Rep., 10, 1213, 10.1038/embor.2009.221 · DOI
  7. Cahan, 2013, Origins and implications of pluripotent stem cell variability and heterogeneity, Nat. Rev. Mol. Cell Biol., 14, 357, 10.1038/nrm3584 · DOI · Paper page
  8. Canham, 2010, Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript, PLoS Biol., 8, e1000379, 10.1371/journal.pbio.1000379 · DOI · Paper page
  9. Chae, 2012, 5-Aminoimidazole-4-carboxyamide ribonucleoside induces G(1)/S arrest and Nanog downregulation via p53 and enhances erythroid differentiation, Stem Cells, 30, 140, 10.1002/stem.778 · DOI
  10. Chambers, 2003, Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells, Cell, 113, 643, 10.1016/S0092-8674(03)00392-1 · DOI · Paper page
  11. Chambers, 2007, Nanog safeguards pluripotency and mediates germline development, Nature, 450, 1230, 10.1038/nature06403 · DOI · Paper page
  12. Chan, 2013, Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast, Cell Stem Cell, 13, 663, 10.1016/j.stem.2013.11.015 · DOI · Paper page
  13. Chen, 2008, Zfp143 regulates Nanog through modulation of Oct4 binding, Stem Cells, 26, 2759, 10.1634/stemcells.2008-0398 · DOI
  14. Cheng, 1998, Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation, Cell, 95, 793, 10.1016/S0092-8674(00)81702-X · DOI · Paper page
  15. Core, 2008, Transcription regulation through promoter-proximal pausing of RNA polymerase II, Science, 319, 1791, 10.1126/science.1150843 · DOI · Paper page
  16. Dan, 2013, Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells, Sci. Rep., 3, 3492, 10.1038/srep03492 · DOI
  17. Dietrich, 2007, Stochastic patterning in the mouse pre-implantation embryo, Development, 134, 4219, 10.1242/dev.003798 · DOI · Paper page
  18. Evans, 1981, Establishment in culture of pluripotential cells from mouse embryos, Nature, 292, 154, 10.1038/292154a0 · DOI · Paper page
  19. Faddah, 2013, Single-cell analysis reveals that expression of nanog is biallelic and equally variable as that of other pluripotency factors in mouse ESCs, Cell Stem Cell, 13, 23, 10.1016/j.stem.2013.04.019 · DOI
  20. Festuccia, 2011, Quantification of pluripotency transcription factor levels in embryonic stem cells by flow cytometry, Curr. Protoc. Stem Cell Biol., 10.1002/9780470151808.sc01b09s19 · DOI
  21. Festuccia, 2012, Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells, Cell Stem Cell, 11, 477, 10.1016/j.stem.2012.08.002 · DOI · Paper page
  22. Festuccia, 2013, The role of pluripotency gene regulatory network components in mediating transitions between pluripotent cell states, Curr. Opin. Genet. Dev., 23, 504, 10.1016/j.gde.2013.06.003 · DOI
  23. Ficz, 2013, FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency, Cell Stem Cell, 13, 351, 10.1016/j.stem.2013.06.004 · DOI · Paper page
  24. Fidalgo, 2012, Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming, Proc. Natl. Acad. Sci. U.S.A., 109, 16202, 10.1073/pnas.1208533109 · DOI
  25. Filipczyk, 2013, Biallelic expression of nanog protein in mouse embryonic stem cells, Cell Stem Cell, 13, 12, 10.1016/j.stem.2013.04.025 · DOI
  26. Frankenberg, 2011, Primitive endoderm differentiates via a three-step mechanism involving Nanog and RTK signaling, Dev. Cell, 21, 1005, 10.1016/j.devcel.2011.10.019 · DOI · Paper page
  27. Gafni, 2013, Derivation of novel human ground state naive pluripotent stem cells, Nature, 504, 282, 10.1038/nature12745 · DOI · Paper page
  28. Garcia, 2013, Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning, Curr. Biol., 23, 2140, 10.1016/j.cub.2013.08.054 · DOI · Paper page
  29. Guo, 2010, Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst, Dev. Cell, 18, 675, 10.1016/j.devcel.2010.02.012 · DOI · Paper page
  30. Habibi, 2013, Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells, Cell Stem Cell, 13, 360, 10.1016/j.stem.2013.06.002 · DOI · Paper page
  31. Hansen, 2013, Allele-specific detection of single mRNA molecules in situ, Nat. Methods, 10, 869, 10.1038/nmeth.2601 · DOI
  32. Harper, 2011, Dynamic analysis of stochastic transcription cycles, PLoS Biol., 9, e1000607, 10.1371/journal.pbio.1000607 · DOI · Paper page
  33. Hatano, 2005, Pluripotential competence of cells associated with Nanog activity, Mech. Dev., 122, 67, 10.1016/j.mod.2004.08.008 · DOI · Paper page
  34. Hayashi, 2008, Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states, Cell Stem Cell, 3, 391, 10.1016/j.stem.2008.07.027 · DOI · Paper page
  35. Jaenisch, 2008, Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming, Cell, 132, 567, 10.1016/j.cell.2008.01.015 · DOI · Paper page
  36. Kalmar, 2009, Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells, PLoS Biol., 7, e1000149, 10.1371/journal.pbio.1000149 · DOI · Paper page
  37. Karwacki-Neisius, 2013, Reduced Oct4 expression directs a robust pluripotent state with distinct signaling activity and increased enhancer occupancy by Oct4 and Nanog, Cell Stem Cell, 12, 531, 10.1016/j.stem.2013.04.023 · DOI · Paper page
  38. Kim, 2008, An extended transcriptional network for pluripotency of embryonic stem cells, Cell, 132, 1049, 10.1016/j.cell.2008.02.039 · DOI · Paper page
  39. Kleinsmith, 1964, Multipotentiality of single embryonal carcinoma cells, Cancer Res., 24, 1544
  40. Kurimoto, 2006, An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis, Nucleic Acids Res., 34, e42, 10.1093/nar/gkl050 · DOI · Paper page
  41. Lackner, 2012, Regulation of transcriptome, translation, and proteome in response to environmental stress in fission yeast, Genome Biol., 13, R25, 10.1186/gb-2012-13-4-r25 · DOI
  42. Leitch, 2013, Naive pluripotency is associated with global DNA hypomethylation, Nat. Struct. Mol. Biol., 20, 311, 10.1038/nsmb.2510 · DOI · Paper page
  43. Levine, 2005, Gene regulatory networks for development, Proc. Natl. Acad. Sci. U.S.A., 102, 4936, 10.1073/pnas.0408031102 · DOI · Paper page
  44. Li, 2011, Central dogma at the single-molecule level in living cells, Nature, 475, 308, 10.1038/nature10315 · DOI · Paper page
  45. Little, 2013, Precise developmental gene expression arises from globally stochastic transcriptional activity, Cell, 154, 789, 10.1016/j.cell.2013.07.025 · DOI · Paper page
  46. Loh, 2006, The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells, Nat. Genet., 38, 431, 10.1038/ng1760 · DOI · Paper page
  47. Luo, 2012, Cell signalling regulates dynamics of Nanog distribution in embryonic stem cell populations, J. R. Soc. Interface, 10, 20120525, 10.1098/rsif.2012.0525 · DOI
  48. MacArthur, 2013, Statistical mechanics of pluripotency, Cell, 154, 484, 10.1016/j.cell.2013.07.024 · DOI · Paper page
  49. MacArthur, 2012, Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity, Nature Cell Biol., 14, 1139, 10.1038/ncb2603 · DOI
  50. Macfarlan, 2011, Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A, Genes Dev., 25, 594, 10.1101/gad.2008511 · DOI · Paper page
  51. Macfarlan, 2012, Embryonic stem cell potency fluctuates with endogenous retrovirus activity, Nature, 487, 57, 10.1038/nature11244 · DOI · Paper page
  52. Marks, 2012, The transcriptional and epigenomic foundations of ground state pluripotency, Cell, 149, 590, 10.1016/j.cell.2012.03.026 · DOI · Paper page
  53. Martin, 1981, Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells, Proc. Natl. Acad. Sci. U.S.A., 78, 7634, 10.1073/pnas.78.12.7634 · DOI · Paper page
  54. Mitsui, 2003, The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells, Cell, 113, 631, 10.1016/S0092-8674(03)00393-3 · DOI · Paper page
  55. Miyanari, 2012, Control of ground-state pluripotency by allelic regulation of Nanog, Nature, 483, 470, 10.1038/nature10807 · DOI
  56. Morgani, 2013, Totipotent embryonic stem cells arise in ground-state culture conditions, Cell Rep., 3, 1945, 10.1016/j.celrep.2013.04.034 · DOI · Paper page
  57. Muramoto, 2012, Live imaging of nascent RNA dynamics reveals distinct types of transcriptional pulse regulation, Proc. Natl. Acad. Sci. U.S.A., 109, 7350, 10.1073/pnas.1117603109 · DOI
  58. Najm, 2011, Isolation of epiblast stem cells from preimplantation mouse embryos, Cell Stem Cell, 8, 318, 10.1016/j.stem.2011.01.016 · DOI
  59. Navarro, 2012, OCT4/SOX2-independent Nanog autorepression modulates heterogeneous Nanog gene expression in mouse ES cells, EMBO J., 31, 4547, 10.1038/emboj.2012.321 · DOI
  60. Nester, 1963, Biosynthetic latency in early stages of deoxyribonucleic acidtransformation in bacillus subtilis, J. Bacteriol., 86, 785, 10.1128/jb.86.4.785-796.1963 · DOI · Paper page
  61. Ng, 2011, The transcriptional and signalling networks of pluripotency, Nat. Cell Biol., 13, 490, 10.1038/ncb0511-490 · DOI · Paper page
  62. Nichols, 2009, Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo, Development, 136, 3215, 10.1242/dev.038893 · DOI · Paper page
  63. Osorno, 2012, The developmental dismantling of pluripotency is reversed by ectopic Oct4 expression, Development, 139, 2288, 10.1242/dev.078071 · DOI · Paper page
  64. Paszek, 2010, Population robustness arising from cellular heterogeneity, Proc. Natl. Acad. Sci. U.S.A., 107, 11644, 10.1073/pnas.0913798107 · DOI
  65. Pauklin, 2013, The cell-cycle state of stem cells determines cell fate propensity, Cell, 155, 135, 10.1016/j.cell.2013.08.031 · DOI · Paper page
  66. Ptashne, 2001, Transcription initiation: imposing specificity by localization, Essays Biochem., 37, 1, 10.1042/bse0370001 · DOI
  67. Raj, 2008, Nature, nurture, or chance: stochastic gene expression and its consequences, Cell, 135, 216, 10.1016/j.cell.2008.09.050 · DOI · Paper page
  68. Ramakrishna, 2011, PEST motif sequence regulating human NANOG for proteasomal degradation, Stem Cells Dev., 20, 1511, 10.1089/scd.2010.0410 · doi:10.1089/scd.2010.0410
  69. Sanchez-Ripoll, 2013, Glycogen synthase kinase-3 inhibition enhances translation of pluripotency-associated transcription factors to contribute to maintenance of mouse embryonic stem cell self-renewal, PLoS ONE, 8, e60148, 10.1371/journal.pone.0060148 · DOI
  70. Sigal, 2006, Variability and memory of protein levels in human cells, Nature, 444, 643, 10.1038/nature05316 · DOI · Paper page
  71. Silva, 2008, Capturing pluripotency, Cell, 132, 532, 10.1016/j.cell.2008.02.006 · DOI · Paper page
  72. Silva, 2009, Nanog is the gateway to the pluripotent ground state, Cell, 138, 722, 10.1016/j.cell.2009.07.039 · DOI · Paper page
  73. Siminovitch, 1963, The distribution of colony-forming cells among spleen colonies, J. Cell. Physiol., 62, 327, 10.1002/jcp.1030620313 · DOI · Paper page
  74. Tesar, 2007, New cell lines from mouse epiblast share defining features with human embryonic stem cells, Nature, 448, 196, 10.1038/nature05972 · DOI · Paper page
  75. Toyooka, 2008, Identification and characterization of subpopulations in undifferentiated ES cell culture, Development, 135, 909, 10.1242/dev.017400 · DOI · Paper page
  76. van den Berg, 2008, The Estrogen Related Receptor Beta interacts with Oct4 to positively regulate Nanog gene expression, Mol. Cell. Biol., 28, 5986, 10.1128/MCB.00301-08 · DOI · Paper page
  77. Williams, 2004, Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1 · Sox2 · Hoxb1-DNA ternary transcription factor complex, J. Biol. Chem., 279, 1449, 10.1074/jbc.M309790200 · DOI · Paper page
  78. Wray, 2011, Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation, Nat. Cell Biol., 13, 838, 10.1038/ncb2267 · DOI · Paper page
  79. Wu, 2013, Distinct allelic patterns of nanog expression impart embryonic stem cell population heterogeneity, PLoS Comput. Biol., 9, e1003140, 10.1371/journal.pcbi.1003140 · DOI
  80. Yamanaka, 2010, FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst, Development, 137, 715, 10.1242/dev.043471 · DOI · Paper page
  81. Zalzman, 2010, Zscan4 regulates telomere elongation and genomic stability in ES cells, Nature, 464, 858, 10.1038/nature08882 · DOI · Paper page

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Metadata

Authors
Torres-Padilla, M.-E., & Chambers, I.
Venue
Development
Publisher
The Company of Biologists
Published
2014-06-01
Volume
141
Issue
11
Pages
2173-2181
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.102624
OpenAlex
W2064805149
Cited by
201
References
10
FWCI
10.83
Type
journal article
Language
en
Open access
hybrid
Licence
creativecommons.org/licenses/by/3.0 (vor, 2288 d)

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Torres-Padilla, M.-E., & Chambers, I. (2014). Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage. Development. https://doi.org/10.1242/dev.102624

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