Ground rules of the pluripotency gene regulatory network (original) (raw)
Ramalho-Santos, M. & Willenbring, H. On the origin of the term “stem cell”. Cell Stem Cell1, 35–38 (2007). CASPubMed Google Scholar
Pappenheim, A. Über Entwicklung und Ausbildung der Erythroblasten. Virchows Arch.145, 587–643 (in German) (1896). Google Scholar
Haeckel, E. Anthropogenie; oder, Entwicklungsgeschichte des Menschen 3rd edn (in German) (Wilhelm Engelmann, 1877). Google Scholar
Evans, M. J. The isolation and properties of a clonal tissue culture strain of pluripotent mouse teratoma cells. J. Embryol. Exp. Morphol.28, 163–176 (1972). CASPubMed Google Scholar
Rosenthal, M. D., Wishnow, R. M. & Sato, G. H. In vitro growth and differentiation of clonal populations of multipotential mouse cells derived from a transplantable testicular teratocarcinoma. J. Natl Cancer Inst.44, 1001–1014 (1970). CASPubMed Google Scholar
Kahan, B. W. & Ephrussi, B. Developmental potentialities of clonal in vitro cultures of mouse testicular teratoma. J. Natl Cancer Inst.44, 1015–1036 (1970). CASPubMed Google Scholar
Finch, B. W. & Ephrussi, B. Retention of multiple developmental potentialities by cells of a mouse testicular teratocarcinoma during prolonged culture in vitro and their extinction upon hybridization with cells of permanent lines. Proc. Natl Acad. Sci. USA57, 615–621 (1967). CASPubMed Google Scholar
Solter, D. From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research. Nat. Rev. Genet.7, 319–327 (2006). CASPubMed Google Scholar
Wu, J., Yamauchi, T. & Izpisua Belmonte, J. C. An overview of mammalian pluripotency. Development143, 1644–1648 (2016). CASPubMed Google Scholar
Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature292, 154–156 (1981). CASPubMed Google Scholar
Martin, G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl Acad. Sci. USA78, 7634–7638 (1981). References 10 and 11 are seminal papers that describe the successful derivation and stable culture of ESCs from mouse blastocysts, thereby 'setting the stage' for the study of the PGRN. CASPubMed Google Scholar
Matsui, Y., Zsebo, K. & Hogan, B. L. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell70, 841–847 (1992). CASPubMed Google Scholar
Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc. Natl Acad. Sci. USA90, 8424–8428 (1993). CASPubMed Google Scholar
Brons, I. G. et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature448, 191–195 (2007). CASPubMed Google Scholar
Tesar, P. J. et al. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature448, 196–199 (2007). References 14 and 15 describe for the first time the derivation of epiSCs, thereby 'setting the stage' for further study of the PGRN. CASPubMed Google Scholar
Huang, Y., Osorno, R., Tsakiridis, A. & Wilson, V. In vivo differentiation potential of epiblast stem cells revealed by chimeric embryo formation. Cell Rep.2, 1571–1578 (2012). CASPubMed Google Scholar
Kojima, Y. et al. The transcriptional and functional properties of mouse epiblast stem cells resemble the anterior primitive streak. Cell Stem Cell14, 107–120 (2014). CASPubMed Google Scholar
Wu, J. et al. An alternative pluripotent state confers interspecies chimaeric competency. Nature521, 316–321 (2015). This paper describes a new type of PSC that selectively integrates into the posterior proximal region of the post-implantation epiblast and can contribute to interspecific chimaeras when injected into the posterior epiblast of post-implantation mouse embryos. CASPubMedPubMed Central Google Scholar
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell126, 663–676 (2006). This paper describes the seminal discovery that PSCs can be induced by reprogramming somatic cells with pluripotency-associated transcription factors. CASPubMed Google Scholar
Gonzalez, F., Boue, S. & Izpisua Belmonte, J. C. Methods for making induced pluripotent stem cells: reprogramming à la carte. Nat. Rev. Genet.12, 231–242 (2011). CASPubMed Google Scholar
Ng, H. H. & Surani, M. A. The transcriptional and signalling networks of pluripotency. Nat. Cell Biol.13, 490–496 (2011). CASPubMed Google Scholar
Scholer, H. R., Hatzopoulos, A. K., Balling, R., Suzuki, N. & Gruss, P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J.8, 2543–2550 (1989). CASPubMedPubMed Central Google Scholar
Nichols, J. et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell95, 379–391 (1998). CASPubMed Google Scholar
Niwa, H., Miyazaki, J. & Smith, A. G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet.24, 372–376 (2000). CASPubMed Google Scholar
Avilion, A. A. et al. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev.17, 126–140 (2003). CASPubMedPubMed Central Google Scholar
Masui, S. et al. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat. Cell Biol.9, 625–635 (2007). CASPubMed Google Scholar
Thomson, M. et al. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell145, 875–889 (2011). CASPubMedPubMed Central Google Scholar
Mitsui, K. et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell113, 631–642 (2003). CASPubMed Google Scholar
Chambers, I. et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell113, 643–655 (2003). CASPubMed Google Scholar
Chambers, I. et al. Nanog safeguards pluripotency and mediates germline development. Nature450, 1230–1234 (2007). CASPubMed Google Scholar
Suzuki, A. et al. Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. Proc. Natl Acad. Sci. USA103, 10294–10299 (2006). CASPubMed Google Scholar
Macarthur, B. D., Ma'ayan, A. & Lemischka, I. R. Systems biology of stem cell fate and cellular reprogramming. Nat. Rev. Mol. Cell Biol.10, 672–681 (2009). CASPubMedPubMed Central Google Scholar
Orkin, S. H. et al. The transcriptional network controlling pluripotency in ES cells. Cold Spring Harb. Symp. Quant. Biol.73, 195–202 (2008). CASPubMed Google Scholar
Hackett, J. A. & Surani, M. A. Regulatory principles of pluripotency: from the ground state up. Cell Stem Cell15, 416–430 (2014). CASPubMed Google Scholar
Adamo, A. et al. LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat. Cell Biol.13, 652–659 (2011). CASPubMed Google Scholar
Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell122, 947–956 (2005). This seminal paper describes the discovery of the genome-wide co-occupancy of OSN, and suggests that the PGRN consists of autoregulatory and feedforward loops. CASPubMedPubMed Central Google Scholar
Chew, J. L. et al. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol. Cell. Biol.25, 6031–6046 (2005). CASPubMedPubMed Central Google Scholar
Rodda, D. J. et al. Transcriptional regulation of Nanog by OCT4 and SOX2. J. Biol. Chem.280, 24731–24737 (2005). CASPubMed Google Scholar
Chen, X. et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell133, 1106–1117 (2008). CASPubMed Google Scholar
Festuccia, N. et al. Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells. Cell Stem Cell11, 477–490 (2012). CASPubMedPubMed Central Google Scholar
Chen, J. et al. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell156, 1274–1285 (2014). CASPubMedPubMed Central Google Scholar
Pan, X. et al. Site-specific disruption of the Oct4–Sox2 interaction reveals coordinated mesendodermal differentiation and the epithelial–mesenchymal transition. J. Biol. Chem.291, 18353–18369 (2016). CASPubMedPubMed Central Google Scholar
Jerabek, S., Merino, F., Scholer, H. R. & Cojocaru, V. OCT4: dynamic DNA binding pioneers stem cell pluripotency. Biochim. Biophys. Acta1839, 138–154 (2014). CASPubMed Google Scholar
Jauch, R. et al. Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells29, 940–951 (2011). CASPubMed Google Scholar
Tapia, N. et al. Dissecting the role of distinct OCT4–SOX2 heterodimer configurations in pluripotency. Sci. Rep.5, 13533 (2015). CASPubMedPubMed Central Google Scholar
Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet.38, 431–440 (2006). CASPubMed Google Scholar
Galonska, C., Ziller, M. J., Karnik, R. & Meissner, A. Ground state conditions induce rapid reorganization of core pluripotency factor binding before global epigenetic reprogramming. Cell Stem Cell17, 462–470 (2015). This paper demonstrates global retargeting of OSN binding and remodelling of the enhancer landscape during the transition between pluripotency states. CASPubMedPubMed Central Google Scholar
Kunarso, G. et al. Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat. Genet.42, 631–634 (2010). CASPubMed Google Scholar
Fort, A. et al. Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nat. Genet.46, 558–566 (2014). CASPubMed Google Scholar
Schmidt, D. et al. Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell148, 335–348 (2012). CASPubMedPubMed Central Google Scholar
Kunath, T. et al. FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development134, 2895–2902 (2007). CASPubMed Google Scholar
Yuan, H., Corbi, N., Basilico, C. & Dailey, L. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev.9, 2635–2645 (1995). CASPubMed Google Scholar
Tee, W. W., Shen, S. S., Oksuz, O., Narendra, V. & Reinberg, D. Erk1/2 activity promotes chromatin features and RNAPII phosphorylation at developmental promoters in mouse ESCs. Cell156, 678–690 (2014). CASPubMedPubMed Central Google Scholar
Niwa, H., Burdon, T., Chambers, I. & Smith, A. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev.12, 2048–2060 (1998). CASPubMedPubMed Central Google Scholar
Niwa, H., Ogawa, K., Shimosato, D. & Adachi, K. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature460, 118–122 (2009). CASPubMed Google Scholar
Martello, G., Bertone, P. & Smith, A. Identification of the missing pluripotency mediator downstream of leukaemia inhibitory factor. EMBO J.32, 2561–2574 (2013). CASPubMedPubMed Central Google Scholar
Ye, S., Li, P., Tong, C. & Ying, Q. L. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1. EMBO J.32, 2548–2560 (2013). CASPubMedPubMed Central Google Scholar
Chen, C. Y. et al. Bcl3 bridges LIF–STAT3 to Oct4 signaling in the maintenance of naive pluripotency. Stem Cells33, 3468–3480 (2015). CASPubMed Google Scholar
Ying, Q. L., Nichols, J., Chambers, I. & Smith, A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell115, 281–292 (2003). CASPubMed Google Scholar
Ying, Q. L. et al. The ground state of embryonic stem cell self-renewal. Nature453, 519–523 (2008). This is the original report of the 2i condition and ground-state pluripotency. CASPubMedPubMed Central Google Scholar
Marks, H. et al. The transcriptional and epigenomic foundations of ground state pluripotency. Cell149, 590–604 (2012). CASPubMedPubMed Central Google Scholar
Boroviak, T., Loos, R., Bertone, P., Smith, A. & Nichols, J. The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification. Nat. Cell Biol.16, 516–528 (2014). CASPubMedPubMed Central Google Scholar
Yeo, J. C. et al. Klf2 is an essential factor that sustains ground state pluripotency. Cell Stem Cell14, 864–872 (2014). CASPubMed Google Scholar
Qiu, D. et al. Klf2 and Tfcp2l1, two Wnt/β-catenin targets, act synergistically to induce and maintain naive pluripotency. Stem Cell Rep.5, 314–322 (2015). CAS Google Scholar
Kim, S. H. et al. ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal. Stem Cell Res.13, 1–11 (2014). CASPubMed Google Scholar
Chen, H. et al. Erk signaling is indispensable for genomic stability and self-renewal of mouse embryonic stem cells. Proc. Natl Acad. Sci. USA112, E5936–E5943 (2015). This study challenges the idea that ERK signalling is dispensable for naive pluripotency by showing that ESCs cannot be maintained following double knockout ofErk1andErk2. CASPubMed Google Scholar
Cole, M. F., Johnstone, S. E., Newman, J. J., Kagey, M. H. & Young, R. A. Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells. Genes Dev.22, 746–755 (2008). CASPubMedPubMed Central Google Scholar
Martello, G. et al. Esrrb is a pivotal target of the Gsk3/Tcf3 axis regulating embryonic stem cell self-renewal. Cell Stem Cell11, 491–504 (2012). CASPubMedPubMed Central Google Scholar
Kagey, M. H. et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature467, 430–435 (2010). CASPubMedPubMed Central Google Scholar
Fazzio, T. G., Huff, J. T. & Panning, B. An RNAi screen of chromatin proteins identifies Tip60-p400 as a regulator of embryonic stem cell identity. Cell134, 162–174 (2008). CASPubMedPubMed Central Google Scholar
Ding, L. et al. Systems analyses reveal shared and diverse attributes of Oct4 regulation in pluripotent cells. Cell Syst.1, 141–151 (2015). CASPubMedPubMed Central Google Scholar
Hu, G. et al. A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal. Genes Dev.23, 837–848 (2009). This paper describes a screen that discovered a large number of new genes in the PGRN and a new PGRN module involving CNOT3, TRIM28 and c-MYC. CASPubMedPubMed Central Google Scholar
Li, M., Liu, G. H. & Izpisua Belmonte, J. C. Navigating the epigenetic landscape of pluripotent stem cells. Nat. Rev. Mol. Cell Biol.13, 524–535 (2012). CASPubMed Google Scholar
Gorkin, D. U., Leung, D. & Ren, B. The 3D genome in transcriptional regulation and pluripotency. Cell Stem Cell14, 762–775 (2014). CASPubMedPubMed Central Google Scholar
Wei, Z. et al. Klf4 organizes long-range chromosomal interactions with the Oct4 locus in reprogramming and pluripotency. Cell Stem Cell13, 36–47 (2013). CASPubMed Google Scholar
Zhang, H. et al. Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming. Cell Stem Cell13, 30–35 (2013). CASPubMed Google Scholar
Phillips-Cremins, J. E. et al. Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell153, 1281–1295 (2013). References 78–80 show that pluripotency-associated genes regulate 3D genome organization, which in turn influences their own expression and cell fate determination. CASPubMedPubMed Central Google Scholar
Rowe, H. M. et al. TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells. Genome Res.23, 452–461 (2013). CASPubMedPubMed Central Google Scholar
Schultz, D. C., Ayyanathan, K., Negorev, D., Maul, G. G. & Rauscher, F. J. 3rd. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev.16, 919–932 (2002). CASPubMedPubMed Central Google Scholar
Cheng, B., Ren, X. & Kerppola, T. K. KAP1 represses differentiation-inducible genes in embryonic stem cells through cooperative binding with PRC1 and derepresses pluripotency-associated genes. Mol. Cell. Biol.34, 2075–2091 (2014). PubMedPubMed Central Google Scholar
Sun, C. et al. Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells. Mol. Cell. Biol.29, 4574–4583 (2009). CASPubMedPubMed Central Google Scholar
Fujii, S. et al. Nr0b1 is a negative regulator of Zscan4c in mouse embryonic stem cells. Sci. Rep.5, 9146 (2015). PubMedPubMed Central Google Scholar
Zhang, J. et al. Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency. Nat. Commun.5, 5042 (2014). CASPubMedPubMed Central Google Scholar
Ding, J. et al. Tex10 coordinates epigenetic control of super-enhancer activity in pluripotency and reprogramming. Cell Stem Cell16, 653–668 (2015). CASPubMedPubMed Central Google Scholar
Leitch, H. G. et al. Naive pluripotency is associated with global DNA hypomethylation. Nat. Struct. Mol. Biol.20, 311–316 (2013). CASPubMedPubMed Central Google Scholar
Yamaji, M. et al. PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. Cell Stem Cell12, 368–382 (2013). CASPubMed Google Scholar
Tu, S. et al. Co-repressor CBFA2T2 regulates pluripotency and germline development. Nature534, 387–390 (2016). PubMedPubMed Central Google Scholar
Tiscornia, G. & Izpisua Belmonte, J. C. MicroRNAs in embryonic stem cell function and fate. Genes Dev.24, 2732–2741 (2010). CASPubMedPubMed Central Google Scholar
Houbaviy, H. B., Murray, M. F. & Sharp, P. A. Embryonic stem cell-specific microRNAs. Dev. Cell5, 351–358 (2003). CASPubMed Google Scholar
Melton, C., Judson, R. L. & Blelloch, R. Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature463, 621–626 (2010). CASPubMedPubMed Central Google Scholar
Li, M. & Izpisua Belmonte, J. C. Roles for noncoding RNAs in cell-fate determination and regeneration. Nat. Struct. Mol. Biol.22, 2–4 (2015). CASPubMed Google Scholar
Gu, K. L. et al. Pluripotency-associated miR-290/302 family of microRNAs promote the dismantling of naive pluripotency. Cell Res.26, 350–366 (2016). CASPubMedPubMed Central Google Scholar
Sheik Mohamed, J., Gaughwin, P. M., Lim, B., Robson, P. & Lipovich, L. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA16, 324–337 (2010). PubMedPubMed Central Google Scholar
Loewer, S. et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat. Genet.42, 1113–1117 (2010). References 97 and 98 highlight the roles of lncRNAs in modulating the PGRN. CASPubMedPubMed Central Google Scholar
Wang, Y. et al. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev. Cell25, 69–80 (2013). CASPubMed Google Scholar
Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. A. & Kosik, K. S. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell137, 647–658 (2009). CASPubMed Google Scholar
Santoni, F. A., Guerra, J. & Luban, J. HERV-H RNA is abundant in human embryonic stem cells and a precise marker for pluripotency. Retrovirology9, 111 (2012). CASPubMedPubMed Central Google Scholar
Lu, X. et al. The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat. Struct. Mol. Biol.21, 423–425 (2014). CASPubMed Google Scholar
Wang, J. et al. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. Nature516, 405–409 (2014). CASPubMed Google Scholar
Salomonis, N. et al. Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc. Natl Acad. Sci. USA107, 10514–10519 (2010). CASPubMed Google Scholar
Gabut, M. et al. An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell147, 132–146 (2011). CASPubMed Google Scholar
Das, S., Jena, S. & Levasseur, D. N. Alternative splicing produces Nanog protein variants with different capacities for self-renewal and pluripotency in embryonic stem cells. J. Biol. Chem.286, 42690–42703 (2011). CASPubMedPubMed Central Google Scholar
Lu, Y. et al. Alternative splicing of MBD2 supports self-renewal in human pluripotent stem cells. Cell Stem Cell15, 92–101 (2014). CASPubMedPubMed Central Google Scholar
Han, H. et al. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature498, 241–245 (2013). References 107 and 108 show the roles of alternative splicing in regulating pluripotency and self-renewal. CASPubMedPubMed Central Google Scholar
Jia, G., Fu, Y. & He, C. Reversible RNA adenosine methylation in biological regulation. Trends Genet.29, 108–115 (2013). CASPubMed Google Scholar
Batista, P. J. et al. m6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell15, 707–719 (2014). CASPubMedPubMed Central Google Scholar
Wang, Y. et al. _N_6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol.16, 191–198 (2014). CASPubMedPubMed Central Google Scholar
Morgani, S. M. et al. Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep.3, 1945–1957 (2013). CASPubMedPubMed Central Google Scholar
Macfarlan, T. S. et al. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature487, 57–63 (2012). CASPubMedPubMed Central Google Scholar
Wu, J. & Izpisua Belmonte, J. C. Dynamic pluripotent stem cell states and their applications. Cell Stem Cell17, 509–525 (2015). CASPubMed Google Scholar
Tonge, P. D. et al. Divergent reprogramming routes lead to alternative stem-cell states. Nature516, 192–197 (2014). CASPubMed Google Scholar
Weinberger, L., Ayyash, M., Novershtern, N. & Hanna, J. H. Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat. Rev. Mol. Cell Biol.17, 155–169 (2016). CASPubMed Google Scholar
Ficz, G. et al. FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell13, 351–359 (2013). CASPubMedPubMed Central Google Scholar
von Meyenn, F. et al. Impairment of DNA methylation maintenance is the main cause of global demethylation in naive embryonic stem cells. Mol. Cell62, 848–861 (2016). CASPubMedPubMed Central Google Scholar
Murakami, K. et al. NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers. Nature529, 403–407 (2016). CASPubMedPubMed Central Google Scholar
Factor, D. C. et al. Epigenomic comparison reveals activation of “seed” enhancers during transition from naive to primed pluripotency. Cell Stem Cell14, 854–863 (2014). CASPubMedPubMed Central Google Scholar
Buecker, C. et al. Reorganization of enhancer patterns in transition from naive to primed pluripotency. Cell Stem Cell14, 838–853 (2014). References 120 and 121 demonstrate the global retargeting of OSN binding and remodelling of the enhancer landscape during the transition between pluripotency states. CASPubMedPubMed Central Google Scholar
Zhang, H. et al. MLL1 inhibition reprograms epiblast stem cells to naive pluripotency. Cell Stem Cell18, 481–494 (2016). CASPubMedPubMed Central Google Scholar
Li, M., Suzuki, K., Kim, N. Y., Liu, G. H. & Izpisua Belmonte, J. C. A cut above the rest: targeted genome editing technologies in human pluripotent stem cells. J. Biol. Chem.289, 4594–4599 (2014). CASPubMed Google Scholar
Suzuki, K. et al. Targeted gene correction minimally impacts whole-genome mutational load in human-disease-specific induced pluripotent stem cell clones. Cell Stem Cell15, 31–36 (2014). CASPubMedPubMed Central Google Scholar
Li, M. et al. Efficient correction of hemoglobinopathy-causing mutations by homologous recombination in integration-free patient iPSCs. Cell Res.21, 1740–1744 (2011). CASPubMedPubMed Central Google Scholar
Li, M. & Izpisua Belmonte, J. C. Looking to the future following 10 years of induced pluripotent stem cell technologies. Nat. Protoc.11, 1579–1585 (2016). CASPubMed Google Scholar
Goolam, M. et al. Heterogeneity in Oct4 and Sox2 targets biases cell fate in 4-cell mouse embryos. Cell165, 61–74 (2016). CASPubMedPubMed Central Google Scholar
Kolodziejczyk, A. A. et al. Single cell RNA-sequencing of pluripotent states unlocks modular transcriptional variation. Cell Stem Cell17, 471–485 (2015). CASPubMedPubMed Central Google Scholar
Angermueller, C. et al. Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity. Nat. Methods13, 229–232 (2016). CASPubMedPubMed Central Google Scholar
Guo, G. et al. Serum-based culture conditions provoke gene expression variability in mouse embryonic stem cells as revealed by single-cell analysis. Cell Rep.14, 956–965 (2016). CASPubMedPubMed Central Google Scholar
de Wit, E. et al. The pluripotent genome in three dimensions is shaped around pluripotency factors. Nature501, 227–231 (2013). CASPubMed Google Scholar
Apostolou, E. et al. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. Cell Stem Cell12, 699–712 (2013). CASPubMedPubMed Central Google Scholar