Display options
Share it on

Cell Mol Life Sci. 2021 Dec;78(23):7339-7353. doi: 10.1007/s00018-021-03975-8. Epub 2021 Oct 26.

Key features of the POU transcription factor Oct4 from an evolutionary perspective.

Cellular and molecular life sciences : CMLS

Evgeny I Bakhmet, Alexey N Tomilin

Affiliations

  1. Laboratory of the Molecular Biology of Stem Cells, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia. [email protected].
  2. Laboratory of the Molecular Biology of Stem Cells, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.

PMID: 34698883 DOI: 10.1007/s00018-021-03975-8

Abstract

Oct4, a class V POU-domain protein that is encoded by the Pou5f1 gene, is thought to be a key transcription factor in the early development of mammals. This transcription factor plays indispensable roles in pluripotent stem cells as well as in the acquisition of pluripotency during somatic cell reprogramming. Oct4 has also been shown to play a role as a pioneer transcription factor during zygotic genome activation (ZGA) from zebrafish to human. However, during the past decade, several studies have brought these conclusions into question. It was clearly shown that the first steps in mouse development are not affected by the loss of Oct4. Subsequently, the role of Oct4 as a genome activator was brought into doubt. It was also found that the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) could proceed without Oct4. In this review, we summarize recent findings, reassess the role of Oct4 in reprogramming and ZGA, and point to structural features that may underlie this role. We speculate that pluripotent stem cells resemble neural stem cells more closely than previously thought. Oct4 orthologs within the POUV class hold key roles in genome activation during early development of species with late ZGA. However, in Placentalia, eutherian-specific proteins such as Dux overtake Oct4 in ZGA and endow them with the formation of an evolutionary new tissue-the placenta.

© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Keywords: ESCs; NSCs; Oct4; Pluripotency; Reprogramming; Zygotic genome activation; iPSCs

References

  1. Schöler HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P (1989) A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J 8:2543–2550. https://doi.org/10.1002/j.1460-2075.1989.tb08392.x - PubMed
  2. Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, Staudt LM (1990) A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature 345:686–692. https://doi.org/10.1038/345686a0 - PubMed
  3. Herr W, Sturm RA, Clerc RG, Corcoran LM, Baltimore D, Sharp PA, Ingraham HA et al (1988) The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. https://doi.org/10.1101/gad.2.12a.1513 - PubMed
  4. Botquin V, Hess H, Fuhrmann G, Anastassiadis C, Gross MK, Vriend G, Schöler HR (1998) New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Genes Dev 12:2073–2090. https://doi.org/10.1101/gad.12.13.2073 - PubMed
  5. Tomilin A, Remenyi A, Lins K, Bak H, Leidel S, Vriend G, Wilmanns M et al (2000) Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell. https://doi.org/10.1016/s0092-8674(00)00189-6 - PubMed
  6. Remenyi A, Tomilin A, Pohl E, Lins K, Philippsen A, Reinbold R, Schöler HR et al (2001) Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping. Mol Cell 8:569–80. https://doi.org/10.1016/s1097-2765(01)00336-7 - PubMed
  7. Remenyi A, Lins K, Nissen LJ, Reinbold R, Scholer HR, Wilmanns M (2003) Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev 17:2048–2059. https://doi.org/10.1101/gad.269303 - PubMed
  8. Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Schöler H et al (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379–391. https://doi.org/10.1016/s0092-8674(00)81769-9 - PubMed
  9. Wu G, Han D, Gong Y, Sebastiano V, Gentile L, Singhal N, Adachi K et al (2013) Establishment of totipotency does not depend on Oct4A. Nat Cell Biol 15:1089–1097. https://doi.org/10.1038/ncb2816 - PubMed
  10. Niwa H, Miyazaki J-I, Smith AG (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24:372–376. https://doi.org/10.1038/74199 - PubMed
  11. Radzisheuskaya A, Chia Gle B, dos Santos RL, Theunissen TW, Castro LF, Nichols J, Silva JC (2013) A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages. Nat Cell Biol 15:579–590. https://doi.org/10.1038/ncb2742 - PubMed
  12. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. https://doi.org/10.1016/j.cell.2006.07.024 - PubMed
  13. An Z, Liu P, Zheng J, Si C, Li T, Chen Y, Ma T et al (2019) Sox2 and Klf4 as the functional core in pluripotency induction without exogenous Oct4. Cell Rep 29(1986–2000):e8. https://doi.org/10.1016/j.celrep.2019.10.026 - PubMed
  14. Velychko S, Adachi K, Kim K-P, Hou Y, MacCarthy CM, Wu G, Schöler HR (2019) Excluding Oct4 from yamanaka cocktail unleashes the developmental potential of iPSCs. Cell Stem Cell. https://doi.org/10.1016/j.stem.2019.10.002 - PubMed
  15. Michael AK, Grand RS, Isbel L, Cavadini S, Kozicka Z, Kempf G, Bunker RD et al (2020) Mechanisms of OCT4-SOX2 motif readout on nucleosomes. Science. https://doi.org/10.1126/science.abb0074 - PubMed
  16. Le Bin GC, Munoz-Descalzo S, Kurowski A, Leitch H, Lou X, Mansfield W, Etienne-Dumeau C et al (2014) Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst. Development 141:1001–1010. https://doi.org/10.1242/dev.096875 - PubMed
  17. Frum T, Halbisen MA, Wang C, Amiri H, Robson P, Ralston A (2013) Oct4 Cell-autonomously promotes primitive endoderm development in the mouse blastocyst. Dev Cell 25:610–622. https://doi.org/10.1016/j.devcel.2013.05.004 - PubMed
  18. Verrijzer CP, Van der Vliet PC (1993) POU domain transcription factors. Biochim Biophys Acta 1173:1–21. https://doi.org/10.1016/0167-4781(93)90237-8 - PubMed
  19. Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO (1994) Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell 77:21–32. https://doi.org/10.1016/0092-8674(94)90231-3 - PubMed
  20. Pan G, Qin B, Liu N, Scholer HR, Pei D (2004) Identification of a nuclear localization signal in OCT4 and generation of a dominant negative mutant by its ablation. J Biol Chem 279:37013–37020. https://doi.org/10.1074/jbc.M405117200 - PubMed
  21. Kong X, Liu J, Li L, Yue L, Zhang L, Jiang H, Xie X et al (2015) Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition. Nucleic Acids Res 43:4381–4392. https://doi.org/10.1093/nar/gkv323 - PubMed
  22. Esch D, Vahokoski J, Groves MR, Pogenberg V, Cojocaru V, Vom Bruch H, Han D et al (2013) A unique Oct4 interface is crucial for reprogramming to pluripotency. Nat Cell Biol 15:295–301. https://doi.org/10.1038/ncb2680 - PubMed
  23. Roberts GA, Ozkan B, Gachulincova I, O’Dwyer MR, Hall-Ponsele E, Saxena M, Robinson PJ et al (2021) Dissecting OCT4 defines the role of nucleosome binding in pluripotency. Nat Cell Biol 23:834–845. https://doi.org/10.1038/s41556-021-00727-5 - PubMed
  24. Jerabek S, Ng CKL, Wu G, Arauzo-Bravo MJ, Kim KP, Esch D, Malik V et al (2016) Changing POU dimerization preferences converts Oct6 into a pluripotency inducer. EMBO Rep 18:319–333. https://doi.org/10.15252/embr.201642958 - PubMed
  25. Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK (1997) Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 11:198–212. https://doi.org/10.1101/gad.11.2.198 - PubMed
  26. Malik V, Glaser LV, Zimmer D, Velychko S, Weng M, Holzner M, Arend M et al (2019) Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2. Nat Commun 10:3477. https://doi.org/10.1038/s41467-019-11054-7 - PubMed
  27. Tan DS, Chen Y, Gao Y, Bednarz A, Wei Y, Malik V, Ho DH et al (2021) Directed evolution of an enhanced POU reprogramming factor for cell fate engineering. Mol Biol Evol. https://doi.org/10.1093/molbev/msab075 - PubMed
  28. Williams DC Jr, Cai M, Clore GM (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 279:1449–1457. https://doi.org/10.1074/jbc.M309790200 - PubMed
  29. Okumura-Nakanishi S, Saito M, Niwa H, Ishikawa F (2005) Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem 280:5307–5317. https://doi.org/10.1074/jbc.M410015200 - PubMed
  30. Yuan H, Corbi N, Basilico C, Dailey L (1995) Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev 9:2635–2645. https://doi.org/10.1101/gad.9.21.2635 - PubMed
  31. Nishimoto M, Fukushima A, Okuda A, Muramatsu M (1999) The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. Mol Cell Biol 19:5453–5465. https://doi.org/10.1128/MCB.19.8.5453 - PubMed
  32. Tomioka M, Nishimoto M, Miyagi S, Katayanagi T, Fukui N, Niwa H, Muramatsu M et al (2002) Identification of Sox-2 regulatory region which is under the control of Oct-3/4-Sox-2 complex. Nucleic Acids Res 30:3202–3213. https://doi.org/10.1093/nar/gkf435 - PubMed
  33. Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P (2005) Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 280:24731–24737. https://doi.org/10.1074/jbc.M502573200 - PubMed
  34. Tapia N, MacCarthy C, Esch D, Gabriele Marthaler A, Tiemann U, Arauzo-Bravo MJ, Jauch R et al (2015) Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci Rep 5:13533. https://doi.org/10.1038/srep13533 - PubMed
  35. Velychko S, Kang K, Kim SM, Kwak TH, Kim KP, Park C, Hong K et al (2019) Fusion of reprogramming factors alters the trajectory of somatic lineage conversion. Cell Rep 27(30–39):e4. https://doi.org/10.1016/j.celrep.2019.03.023 - PubMed
  36. Leichsenring M, Maes J, Mossner R, Driever W, Onichtchouk D (2013) Pou5f1 transcription factor controls zygotic gene activation in vertebrates. Science 341:1005–1009. https://doi.org/10.1126/science.1242527 - PubMed
  37. Mistri TK, Devasia AG, Chu LT, Ng WP, Halbritter F, Colby D, Martynoga B et al (2015) Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells. EMBO Rep 16:1177–1191. https://doi.org/10.15252/embr.201540467 - PubMed
  38. Chen J, Zhang Z, Li L, Chen BC, Revyakin A, Hajj B, Legant W et al (2014) Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156:1274–1285. https://doi.org/10.1016/j.cell.2014.01.062 - PubMed
  39. Nishimoto M, Miyagi S, Yamagishi T, Sakaguchi T, Niwa H, Muramatsu M, Okuda A (2005) Oct-3/4 maintains the proliferative embryonic stem cell state via specific binding to a variant octamer sequence in the regulatory region of the UTF1 locus. Mol Cell Biol 25:5084–5094. https://doi.org/10.1128/MCB.25.12.5084-5094.2005 - PubMed
  40. Pan X, Cang X, Dan S, Li J, Cheng J, Kang B, Duan X et al (2016) Site-specific disruption of the Oct4/Sox2 protein interaction reveals coordinated mesendodermal differentiation and the epithelial-mesenchymal transition. J Biol Chem 291:18353–18369. https://doi.org/10.1074/jbc.M116.745414 - PubMed
  41. Aksoy I, Jauch R, Chen J, Dyla M, Divakar U, Bogu GK, Teo R et al (2013) Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. EMBO J 32:938–953. https://doi.org/10.1038/emboj.2013.31 - PubMed
  42. Jauch R, Aksoy I, Hutchins AP, Ng CK, Tian XF, Chen J, Palasingam P et al (2011) Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells 29:940–951. https://doi.org/10.1002/stem.639 - PubMed
  43. Merino F, Ng CKL, Veerapandian V, Scholer HR, Jauch R, Cojocaru V (2014) Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation. Structure 22:1274–1286. https://doi.org/10.1016/j.str.2014.06.014 - PubMed
  44. Niwa H, Sekita Y, Trend-Ayush E, Grützner F (2008) Platypus Pou5f1 reveals the first steps in the evolution of trophectoderm differentiation and pluripotency in mammals. Evol Dev 10:671–682. https://doi.org/10.1111/j.1525-142X.2008.00280.x - PubMed
  45. Lavial F, Acloque H, Bertocchini F, Macleod DJ, Boast S, Bachelard E, Montillet G et al (2007) The Oct4 homologue PouV and Nanog regulate pluripotency in chicken embryonic stem cells. Development 134:3549–3563. https://doi.org/10.1242/dev.006569 - PubMed
  46. Morrison GM, Brickman JM (2006) Conserved roles for Oct4 homologues in maintaining multipotency during early vertebrate development. Development 133:2011–2022. https://doi.org/10.1242/dev.02362 - PubMed
  47. Onichtchouk D, Geier F, Polok B, Messerschmidt DM, Mossner R, Wendik B, Song S et al (2010) Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development. Mol Syst Biol 6:354. https://doi.org/10.1038/msb.2010.9 - PubMed
  48. Tapia N, Reinhardt P, Duemmler A, Wu G, Arauzo-Bravo MJ, Esch D, Greber B et al (2012) Reprogramming to pluripotency is an ancient trait of vertebrate Oct4 and Pou2 proteins. Nat Commun 3:1279. https://doi.org/10.1038/ncomms2229 - PubMed
  49. Niwa H, Nakamura A, Urata M, Shirae-Kurabayashi M, Kuraku S, Russell S, Ohtsuka S (2016) The evolutionally-conserved function of group B1 Sox family members confers the unique role of Sox2 in mouse ES cells. BMC Evol Biol 16:173. https://doi.org/10.1186/s12862-016-0755-4 - PubMed
  50. Gentsch GE, Spruce T, Owens NDL, Smith JC (2019) Maternal pluripotency factors initiate extensive chromatin remodelling to predefine first response to inductive signals. Nat Commun 10:4269. https://doi.org/10.1038/s41467-019-12263-w - PubMed
  51. Onichtchouk D, Driever W (2016) Zygotic genome activators, developmental timing, and pluripotency. Curr Top Dev Biol 116:273–297. https://doi.org/10.1016/bs.ctdb.2015.12.004 - PubMed
  52. Okuda Y, Ogura E, Kondoh H, Kamachi Y (2010) B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo. PLoS Genet 6:e1000936. https://doi.org/10.1371/journal.pgen.1000936 - PubMed
  53. Kobayashi K, Khan A, Ikeda M, Nakamoto A, Maekawa M, Yamasu K (2018) In vitro analysis of the transcriptional regulatory mechanism of zebrafish pou5f3. Exp Cell Res 364:28–41. https://doi.org/10.1016/j.yexcr.2018.01.023 - PubMed
  54. Fernandez-Tresguerres B, Canon S, Rayon T, Pernaute B, Crespo M, Torroja C, Manzanares M (2010) Evolution of the mammalian embryonic pluripotency gene regulatory network. Proc Natl Acad Sci USA 107:19955–19960. https://doi.org/10.1073/pnas.1010708107 - PubMed
  55. Han JY, Lee HG, Park YH, Hwang YS, Kim SK, Rengaraj D, Cho BW et al (2018) Acquisition of pluripotency in the chick embryo occurs during intrauterine embryonic development via a unique transcriptional network. J Anim Sci Biotechnol 9:31. https://doi.org/10.1186/s40104-018-0246-0 - PubMed
  56. Brumbaugh J, Hou Z, Russell JD, Howden SE, Yu P, Ledvina AR, Coon JJ et al (2012) Phosphorylation regulates human OCT4. Proc Natl Acad Sci USA 109:7162–7168. https://doi.org/10.1073/pnas.1203874109 - PubMed
  57. Saxe JP, Tomilin A, Scholer HR, Plath K, Huang J (2009) Post-translational regulation of Oct4 transcriptional activity. PLoS One 4:e4467. https://doi.org/10.1371/journal.pone.0004467 - PubMed
  58. Abulaiti X, Zhang H, Wang A, Li N, Li Y, Wang C, Du X et al (2017) Phosphorylation of threonine(343) Is crucial for OCT4 interaction with SOX2 in the maintenance of mouse embryonic stem cell pluripotency. Stem Cell Rep 9:1630–1641. https://doi.org/10.1016/j.stemcr.2017.09.001 - PubMed
  59. Bae KB, Yu DH, Lee KY, Yao K, Ryu J, Lim DY, Zykova TA et al (2017) Serine 347 phosphorylation by JNKs negatively regulates OCT4 protein stability in mouse embryonic stem cells. Stem Cell Rep 9:2050–2064. https://doi.org/10.1016/j.stemcr.2017.10.017 - PubMed
  60. Lin Y, Yang Y, Li W, Chen Q, Li J, Pan X, Zhou L et al (2012) Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells. Mol Cell 48:627–640. https://doi.org/10.1016/j.molcel.2012.08.030 - PubMed
  61. Spelat R, Ferro F, Curcio F (2012) Serine 111 phosphorylation regulates OCT4A protein subcellular distribution and degradation. J Biol Chem 287:38279–38288. https://doi.org/10.1074/jbc.M112.386755 - PubMed
  62. Wei F, Scholer HR, Atchison ML (2007) Sumoylation of Oct4 enhances its stability, DNA binding, and transactivation. J Biol Chem 282:21551–21560. https://doi.org/10.1074/jbc.M611041200 - PubMed
  63. Liao B, Jin Y (2010) Wwp2 mediates Oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner. Cell Res 20:332–344. https://doi.org/10.1038/cr.2009.136 - PubMed
  64. Swaney DL, Wenger CD, Thomson JA, Coon JJ (2009) Human embryonic stem cell phosphoproteome revealed by electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci USA 106:995–1000. https://doi.org/10.1073/pnas.0811964106 - PubMed
  65. Tolkunova E, Malashicheva A, Parfenov VN, Sustmann C, Grosschedl R, Tomilin A (2007) PIAS proteins as repressors of Oct4 function. J Mol Biol 374:1200–1212. https://doi.org/10.1016/j.jmb.2007.09.081 - PubMed
  66. Jukam D, Shariati SAM, Skotheim JM (2017) Zygotic genome activation in vertebrates. Dev Cell 42:316–332. https://doi.org/10.1016/j.devcel.2017.07.026 - PubMed
  67. Schulz KN, Harrison MM (2019) Mechanisms regulating zygotic genome activation. Nat Rev Genet 20:221–234. https://doi.org/10.1038/s41576-018-0087-x - PubMed
  68. Zaret KS, Carroll JS (2011) Pioneer transcription factors: establishing competence for gene expression. Genes Dev 25:2227–2241. https://doi.org/10.1101/gad.176826.111 - PubMed
  69. Soufi A, Garcia MF, Jaroszewicz A, Osman N, Pellegrini M, Zaret KS (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161:555–568. https://doi.org/10.1016/j.cell.2015.03.017 - PubMed
  70. Zhu F, Farnung L, Kaasinen E, Sahu B, Yin Y, Wei B, Dodonova SO et al (2018) The interaction landscape between transcription factors and the nucleosome. Nature 562:76–81. https://doi.org/10.1038/s41586-018-0549-5 - PubMed
  71. Veil M, Yampolsky LY, Gruning B, Onichtchouk D (2019) Pou5f3, SoxB1, and Nanog remodel chromatin on high nucleosome affinity regions at zygotic genome activation. Genome Res 29:383–395. https://doi.org/10.1101/gr.240572.118 - PubMed
  72. Lee MT, Bonneau AR, Takacs CM, Bazzini AA, DiVito KR, Fleming ES, Giraldez AJ (2013) Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Nature 503:360–364. https://doi.org/10.1038/nature12632 - PubMed
  73. Mirny LA (2010) Nucleosome-mediated cooperativity between transcription factors. Proc Natl Acad Sci USA 107:22534–22539. https://doi.org/10.1073/pnas.0913805107 - PubMed
  74. Meers MP, Janssens DH, Henikoff S (2019) Pioneer factor-nucleosome binding events during differentiation are motif encoded. Mol Cell. https://doi.org/10.1016/j.molcel.2019.05.025 - PubMed
  75. Chronis C, Fiziev P, Papp B, Butz S, Bonora G, Sabri S, Ernst J et al (2017) Cooperative binding of transcription factors orchestrates reprogramming. Cell. https://doi.org/10.1016/j.cell.2016.12.016 - PubMed
  76. Liu G, Wang W, Hu S, Wang X, Zhang Y (2018) Inherited DNA methylation primes the establishment of accessible chromatin during genome activation. Genome Res 28:998–1007. https://doi.org/10.1101/gr.228833.117 - PubMed
  77. King HW, Klose RJ (2017) The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells. Elife. https://doi.org/10.7554/eLife.22631 - PubMed
  78. Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E et al (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133:1106–1117. https://doi.org/10.1016/j.cell.2008.04.043 - PubMed
  79. Stadhouders R, Vidal E, Serra F, Di Stefano B, Le Dily F, Quilez J, Gomez A et al (2018) Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming. Nat Genet 50:238–249. https://doi.org/10.1038/s41588-017-0030-7 - PubMed
  80. Di Stefano B, Sardina JL, van Oevelen C, Collombet S, Kallin EM, Vicent GP, Lu J et al (2014) C/EBPalpha poises B cells for rapid reprogramming into induced pluripotent stem cells. Nature 506:235–239. https://doi.org/10.1038/nature12885 - PubMed
  81. Palfy M, Schulze G, Valen E, Vastenhouw NL (2020) Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation. PLoS Genet 16:e1008546. https://doi.org/10.1371/journal.pgen.1008546 - PubMed
  82. Wu J, Xu J, Liu B, Yao G, Wang P, Lin Z, Huang B et al (2018) Chromatin analysis in human early development reveals epigenetic transition during ZGA. Nature 557:256–260. https://doi.org/10.1038/s41586-018-0080-8 - PubMed
  83. Lu F, Liu Y, Inoue A, Suzuki T, Zhao K, Zhang Y (2016) Establishing chromatin regulatory landscape during mouse preimplantation development. Cell 165:1375–1388. https://doi.org/10.1016/j.cell.2016.05.050 - PubMed
  84. Simandi Z, Horvath A, Wright LC, Cuaranta-Monroy I, De Luca I, Karolyi K, Sauer S et al (2016) OCT4 acts as an integrator of pluripotency and signal-induced differentiation. Mol Cell 63:647–661. https://doi.org/10.1016/j.molcel.2016.06.039 - PubMed
  85. Flach G, Johnson MH, Braude PR, Taylor RA, Bolton VN (1982) The transition from maternal to embryonic control in the 2-cell mouse embryo. EMBO J 1:681–686. https://doi.org/10.1002/j.1460-2075.1982.tb01230.x - PubMed
  86. Dobson AT, Raja R, Abeyta MJ, Taylor T, Shen S, Haqq C, Pera RA (2004) The unique transcriptome through day 3 of human preimplantation development. Hum Mol Genet 13:1461–1470. https://doi.org/10.1093/hmg/ddh157 - PubMed
  87. Palmieri SL, Peter W, Hess H, Scholer HR (1994) Oct-4 transcription factor is differentially expressed in the mouse embryo during establishment of the first two extraembryonic cell lineages involved in implantation. Dev Biol 166:259–267. https://doi.org/10.1006/dbio.1994.1312 - PubMed
  88. Khan DR, Dube D, Gall L, Peynot N, Ruffini S, Laffont L, Le Bourhis D et al (2012) Expression of pluripotency master regulators during two key developmental transitions: EGA and early lineage specification in the bovine embryo. PLoS One 7:e34110. https://doi.org/10.1371/journal.pone.0034110 - PubMed
  89. Niakan KK, Eggan K (2013) Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev Biol 375:54–64. https://doi.org/10.1016/j.ydbio.2012.12.008 - PubMed
  90. Blakeley P, Fogarty NM, Del Valle I, Wamaitha SE, Hu TX, Elder K, Snell P et al (2015) Defining the three cell lineages of the human blastocyst by single-cell RNA-seq. Development 142:3613. https://doi.org/10.1242/dev.131235 - PubMed
  91. Gao L, Wu K, Liu Z, Yao X, Yuan S, Tao W, Yi L et al (2018) Chromatin accessibility landscape in human early embryos and its association with evolution. Cell 173(248–259):e15. https://doi.org/10.1016/j.cell.2018.02.028 - PubMed
  92. Hendrickson PG, Dorais JA, Grow EJ, Whiddon JL, Lim JW, Wike CL, Weaver BD et al (2017) Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nat Genet 49:925–934. https://doi.org/10.1038/ng.3844 - PubMed
  93. De Iaco A, Planet E, Coluccio A, Verp S, Duc J, Trono D (2017) DUX-family transcription factors regulate zygotic genome activation in placental mammals. Nat Genet 49:941–945. https://doi.org/10.1038/ng.3858 - PubMed
  94. Yang F, Huang X, Zang R, Chen J, Fidalgo M, Sanchez-Priego C, Yang J et al (2020) DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state. Cell Stem Cell 26(234–250):e7. https://doi.org/10.1016/j.stem.2020.01.004 - PubMed
  95. Macfarlan TS, Gifford WD, Driscoll S, Lettieri K, Rowe HM, Bonanomi D, Firth A et al (2012) Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487:57–63. https://doi.org/10.1038/nature11244 - PubMed
  96. Eckersley-Maslin M, Alda-Catalinas C, Blotenburg M, Kreibich E, Krueger C, Reik W (2019) Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program. Genes Dev 33:194–208. https://doi.org/10.1101/gad.321174.118 - PubMed
  97. Stirparo GG, Kurowski A, Yanagida A, Bates LE, Strawbridge SE, Hladkou S, Stuart HT et al (2021) OCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.2008890118 - PubMed
  98. Fogarty NME, McCarthy A, Snijders KE, Powell BE, Kubikova N, Blakeley P, Lea R et al (2017) Genome editing reveals a role for OCT4 in human embryogenesis. Nature 550:67–73. https://doi.org/10.1038/nature24033 - PubMed
  99. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. https://doi.org/10.1016/j.cell.2007.11.019 - PubMed
  100. Heng JC, Feng B, Han J, Jiang J, Kraus P, Ng JH, Orlov YL et al (2010) The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 6:167–174. https://doi.org/10.1016/j.stem.2009.12.009 - PubMed
  101. Buganim Y, Markoulaki S, van Wietmarschen N, Hoke H, Wu T, Ganz K, Akhtar-Zaidi B et al (2014) The developmental potential of iPSCs is greatly influenced by reprogramming factor selection. Cell Stem Cell 15:295–309. https://doi.org/10.1016/j.stem.2014.07.003 - PubMed
  102. Gao Y, Chen J, Li K, Wu T, Huang B, Liu W, Kou X et al (2013) Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming. Cell Stem Cell 12:453–469. https://doi.org/10.1016/j.stem.2013.02.005 - PubMed
  103. Han DW, Tapia N, Hermann A, Hemmer K, Hoing S, Arauzo-Bravo MJ, Zaehres H et al (2012) Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell 10:465–472. https://doi.org/10.1016/j.stem.2012.02.021 - PubMed
  104. Kim KP, Wu Y, Yoon J, Adachi K, Wu G, Velychko S, MacCarthy CM et al (2020) Reprogramming competence of OCT factors is determined by transactivation domains. Sci Adv. https://doi.org/10.1126/sciadv.aaz7364 - PubMed
  105. Kim KP, Choi J, Yoon J, Bruder JM, Shin B, Kim J, Arauzo-Bravo MJ et al (2021) Permissive epigenomes endow reprogramming competence to transcriptional regulators. Nat Chem Biol 17:47–56. https://doi.org/10.1038/s41589-020-0618-6 - PubMed
  106. Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP et al (2014) Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 15:471–487. https://doi.org/10.1016/j.stem.2014.07.002 - PubMed
  107. Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F, Oxley D et al (2014) Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 158:1254–1269. https://doi.org/10.1016/j.cell.2014.08.029 - PubMed
  108. Thier M, Worsdorfer P, Lakes YB, Gorris R, Herms S, Opitz T, Seiferling D et al (2012) Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell 10:473–479. https://doi.org/10.1016/j.stem.2012.03.003 - PubMed
  109. Kim JB, Sebastiano V, Wu G, Arauzo-Bravo MJ, Sasse P, Gentile L, Ko K et al (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136:411–419. https://doi.org/10.1016/j.cell.2009.01.023 - PubMed
  110. Choi HW, Kim JS, Choi S, Hong YJ, Kim MJ, Seo HG, Do JT (2014) Neural stem cells differentiated from iPS cells spontaneously regain pluripotency. Stem Cells 32:2596–2604. https://doi.org/10.1002/stem.1757 - PubMed
  111. Wurmser AE, Nakashima K, Summers RG, Toni N, D’Amour KA, Lie DC, Gage FH (2004) Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 430:350–356. https://doi.org/10.1038/nature02604 - PubMed
  112. Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlström H, Lendahl U et al (2000) Generalized potential of adult neural stem cells. Science 288:1660–1663. https://doi.org/10.1126/science.288.5471.1660 - PubMed
  113. Galli R, Borello U, Gritti A, Minasi MG, Bjornson CR, Coletta M, Mora M et al (2000) Skeletal myogenic potential of human and mouse neural stem cells. Nat Neurosci 3:986–991. https://doi.org/10.1038/79924 - PubMed
  114. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283:534–537. https://doi.org/10.1126/science.283.5401.534 - PubMed
  115. Zalc A, Sinha R, Gulati GS, Wesche DJ, Daszczuk P, Swigut T, Weissman IL et al (2021) Reactivation of the pluripotency program precedes formation of the cranial neural crest. Science. https://doi.org/10.1126/science.abb4776 - PubMed
  116. Cherepanova OA, Gomez D, Shankman LS, Swiatlowska P, Williams J, Sarmento OF, Alencar GF et al (2016) Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. Nat Med 22:657–665. https://doi.org/10.1038/nm.4109 - PubMed

Publication Types

Grant support