Pluripotent stem cells can be isolated from embryos or derived by reprogramming. Pluripotency is stabilized by an interconnected network of pluripotency genes that cooperatively regulate gene expression. Here we describe the molecular principles of pluripotency gene function and highlight post-transcriptional controls, particularly those induced by RNA-binding proteins and alternative splicing, as an important regulatory layer of pluripotency. We also discuss heterogeneity in pluripotency regulation, alternative pluripotency states and future directions of pluripotent stem cell research.
Subscribe to Journal
Get full journal access for 1 year
only $17.42 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
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).
Rosenthal, M. D., Wishnow, R. M. & Sato, G. H. In vitro growth and differetiation of clonal populations of multipotential mouse clls derived from a transplantable testicular teratocarcinoma. J. Natl. Cancer I. 44, 1001–1014 (1970).
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. USA 57, 615–621 (1967).
Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154–156 (1981).
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. USA 78, 7634–7638 (1981).
Li, M. & Belmonte, J. C. Ground rules of the pluripotency gene regulatory network. Nat. Rev. 18, 180–191 (2017).
Ng, H. H. & Surani, M. A. The transcriptional and signalling networks of pluripotency. Nat. Cell Biol. 13, 490–496 (2011).
Nichols, J. et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95, 379–391 (1998).
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).
Mitsui, K. et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631–642 (2003).
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).
Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947–956 (2005).
Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. 38, 431–440 (2006).
Smith, A. G. et al. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688–690 (1988).
Shu, J. et al. Induction of pluripotency in mouse somatic cells with lineage specifiers. Cell 153, 963–975 (2013).
Montserrat, N. et al. Reprogramming of human fibroblasts to pluripotency with lineage specifiers. Cell Stem Cell 13, 341–350 (2013).
Wu, J., Yamauchi, T. & Izpisua Belmonte, J. C. An overview of mammalian pluripotency. Development 143, 1644–1648 (2016).
Wu, J. & Izpisua Belmonte, J. C. Dynamic pluripotent stem cell states and their applications. Cell Stem Cell 17, 509–525 (2015).
Hayashi, K., Lopes, S. M., Tang, F. & Surani, M. A. Dynamic equilibrium and heterogeneity of mouse pluripotent stem cells with distinct functional and epigenetic states. Cell Stem Cell 3, 391–401 (2008).
Kalmar, T. et al. Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells. PLoS Biol. 7, e1000149 (2009).
MacArthur, B. D. et al. Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity. Nat. Cell Biol. 14, 1139–1147 (2012).
Karwacki-Neisius, V. et al. Reduced Oct4 expression directs a robust pluripotent state with distinct signaling activity and increased enhancer occupancy by Oct4 and Nanog. Cell Stem Cell 12, 531–545 (2013).
Reynolds, N. et al. NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment. Cell Stem Cell 10, 583–594 (2012).
Kumar, R. M. et al. Deconstructing transcriptional heterogeneity in pluripotent stem cells. Nature 516, 56–61 (2014).
Young, R. A. Control of the embryonic stem cell state. Cell 144, 940–954 (2011).
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).
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).
Thomson, M. et al. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell 145, 875–889 (2011).
Takahashi, K. & Yamanaka, S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat. Rev. Mol. Cell Biol. 17, 183–193 (2016).
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).
Avilion, A. A. et al. Multipotent cell lineages in early mouse development depend on SOX2 function. Gen. Dev. 17, 126–140 (2003).
Chew, J. L. et al. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol. Cell. Bio. 25, 6031–6046 (2005).
Rodda, D. J. et al. Transcriptional regulation of nanog by OCT4 and SOX2. J. Biol. Chem. 280, 24731–24737 (2005).
Buganim, Y. et al. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell 150, 1209–1222 (2012).
Chambers, I. et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643–655 (2003).
Chen, X. et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106–1117 (2008).
Festuccia, N. et al. Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells. Cell Stem Cell 11, 477–490 (2012).
Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).
Jerabek, S. et al. Changing POU dimerization preferences converts Oct6 into a pluripotency inducer. EMBO Rep. 18, 319–333 (2017).
Tapia, N. et al. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency. Sci. Rep. 5, 13533 (2015).
Jauch, R. et al. Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells 29, 940–951 (2011).
Ng, C. K. et al. Deciphering the Sox-Oct partner code by quantitative cooperativity measurements. Nucleic Acids Res. 40, 4933–4941 (2012).
Aksoy, I. et al. Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. EMBO J. 32, 938–953 (2013).
Aksoy, I. et al. Sox transcription factors require selective interactions with Oct4 and specific transactivation functions to mediate reprogramming. Stem Cells 31, 2632–2646 (2013).
Mistri, T. K. et al. Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells. EMBO Rep. 16, 1177–1191 (2015).
Zaret, K. S. & Carroll, J. S. Pioneer transcription factors: establishing competence for gene expression. Gen. Dev. 25, 2227–2241 (2011).
Soufi, A., Donahue, G. & Zaret, K. S. Facilitators and impediments of the pluripotency reprogramming factors’ initial engagement with the genome. Cell 151, 994–1004 (2012).
King, H. W. & Klose, R. J. The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells. eLife 6, e22631 (2017).
Singhal, N. et al. Chromatin-remodeling components of the BAF complex facilitate reprogramming. Cell 141, 943–955 (2010).
Esch, D. et al. A unique Oct4 interface is crucial for reprogramming to pluripotency. Nat. Cell Biol. 15, 295–301 (2013).
Sherwood, R. I. et al. Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape. Nat. Biotechnol. 32, 171–178 (2014).
Chronis, C. et al. Cooperative binding of transcription factors orchestrates reprogramming. Cell 168, 442–459 (2017).
Chen, J. et al. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156, 1274–1285 (2014).
White, M. D. et al. Long-lived binding of Sox2 to DNA predicts cell fate in the four-cell mouse embryo. Cell 165, 75–87 (2016).
Dietrich, J. E. & Hiiragi, T. Stochastic patterning in the mouse pre-implantation embryo. Development 134, 4219–4231 (2007).
Kadauke, S. et al. Tissue-specific mitotic bookmarking by hematopoietic transcription factor GATA1. Cell 150, 725–737 (2012).
Caravaca, J. M. et al. Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes. Gen. Dev. 27, 251–260 (2013).
Festuccia, N. et al. Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network. Nat. Cell Biol. 18, 1139–1148 (2016).
Konig, J., Zarnack, K., Luscombe, N. M. & Ule, J. Protein-RNA interactions: new genomic technologies and perspectives. Nat. Rev. 13, 77–83 (2012).
Kwon, S. C. et al. The RNA-binding protein repertoire of embryonic stem cells. Nat. Struct. Mol. Biol. 20, 1122–1130 (2013).
Kim, J. et al. A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 143, 313–324 (2010).
He, C. et al. High-resolution mapping of RNA-binding regions in the nuclear proteome of embryonic stem cells. Mol. Cell 64, 416–430 (2016).
Tsanov, K. M. et al. LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency. Nat. Cell Biol. 19, 60–67 (2017).
Zhang, J. et al. LIN28 regulates stem cell metabolism and conversion to primed pluripotency. Cell Stem Cell 19, 66–80 (2016).
Xu, B., Zhang, K. & Huang, Y. Lin28 modulates cell growth and associates with a subset of cell cycle regulator mRNAs in mouse embryonic stem cells. RNA 15, 357–361 (2009).
Peng, S. et al. Genome-wide studies reveal that Lin28 enhances the translation of genes important for growth and survival of human embryonic stem cells. Stem Cells 29, 496–504 (2011).
Moss, E. G., Lee, R. C. & Ambros, V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88, 637–646 (1997).
Shyh-Chang, N. & Daley, G. Q. Lin28: primal regulator of growth and metabolism in stem cells. Cell Stem Cell 12, 395–406 (2013).
Viswanathan, S. R., Daley, G. Q. & Gregory, R. I. Selective blockade of microRNA processing by Lin28. Science 320, 97–100 (2008).
Parisi, S. et al. Lin28 is induced in primed embryonic stem cells and regulates let-7-independent events. FASEB J. 31, 1046–1058 (2017).
Zhang, J., Nuebel, E., Daley, G. Q., Koehler, C. M. & Teitell, M. A. Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal. Cell Stem Cell 11, 589–595 (2012).
Folmes, C. D. et al. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 14, 264–271 (2011).
Sperber, H. et al. The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition. Nat. Cell Biol. 17, 1523–1535 (2015).
Carbognin, E., Betto, R. M., Soriano, M. E., Smith, A. G. & Martello, G. Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency. EMBO J. 35, 618–634 (2016).
Guo, L. et al. Stat3-coordinated Lin-28-let-7-HMGA2 and miR-200-ZEB1 circuits initiate and maintain oncostatin M-driven epithelial-mesenchymal transition. Oncogene 32, 5272–5282 (2013).
Kalsotra, A. & Cooper, T. A. Functional consequences of developmentally regulated alternative splicing. Nat. Rev. 12, 715–729 (2011).
Salomonis, N. et al. Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc. Natl Acad. Sci. USA 107, 10514–10519 (2010).
Gabut, M. et al. An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell 147, 132–146 (2011).
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).
Cieply, B. et al. Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA-binding proteins. Cell Rep. 15, 247–255 (2016).
Ying, Q. L. et al. The ground state of embryonic stem cell self-renewal. Nature 453, 519–523 (2008).
Wu, J. et al. An alternative pluripotent state confers interspecies chimaeric competency. Nature 521, 316–321 (2015).
Brons, I. G. et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191–195 (2007).
Klein, A. M. et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187–1201 (2015).
Macfarlan, T. S. et al. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487, 57–63 (2012).
Chambers, I. et al. Nanog safeguards pluripotency and mediates germline development. Nature 450, 1230–1234 (2007).
Kolodziejczyk, A. A. et al. Single cell RNA-sequencing of pluripotent states unlocks modular transcriptional variation. Cell Stem Cell 17, 471–485 (2015).
Wu, A. R., Wang, J., Streets, A. M. & Huang, Y. Single-cell transcriptional analysis. Annu. Rev. Anal. Chem. 10, 439–462 (2017).
Zunder, E. R., Lujan, E., Goltsev, Y., Wernig, M. & Nolan, G. P. A continuous molecular roadmap to iPSC reprogramming through progression analysis of single-cell mass cytometry. Cell Stem Cell 16, 323–337 (2015).
Lujan, E. et al. Early reprogramming regulators identified by prospective isolation and mass cytometry. Nature 521, 352–356 (2015).
Angermueller, C. et al. Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity. Nat. Methods 13, 229–232 (2016).
Dey, S. S., Kester, L., Spanjaard, B., Bienko, M. & van Oudenaarden, A. Integrated genome and transcriptome sequencing of the same cell. Nat. Biotechnol. 33, 285–289 (2015).
Guo, F. et al. Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells. Cell Res. 27, 967–988 (2017).
Hou, Y. et al. Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res. 26, 304–319 (2016).
Hu, Y. et al. Simultaneous profiling of transcriptome and DNA methylome from a single cell. Genome Biol. 17, 88 (2016).
Macaulay, I. C. et al. G&T-seq: parallel sequencing of single-cell genomes and transcriptomes. Nat. Methods 12, 519–522 (2015).
Toyooka, Y., Shimosato, D., Murakami, K., Takahashi, K. & Niwa, H. Identification and characterization of subpopulations in undifferentiated ES cell culture. Development 135, 909–918 (2008).
Smith, R. C. G. et al. Nanog fluctuations in embryonic stem cells highlight the problem of measurement in cell biology. Biophys. J. 112, 2641–2652 (2017).
Faddah, D. A. et al. 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, 23–29 (2013).
Petropoulos, S. et al. Single-cell RNA-seq reveals lineage and X chromosome dynamics in human preimplantation embryos. Cell 165, 1012–1026 (2016).
Cockburn, K. & Rossant, J. Making the blastocyst: lessons from the mouse. J. Clin. Invest. 120, 995–1003 (2010).
Yamanaka, Y., Lanner, F. & Rossant, J. FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137, 715–724 (2010).
Gafni, O. et al. Derivation of novel human ground state naive pluripotent stem cells. Nature 504, 282–286 (2013).
Chan, Y. S. et al. Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast. Cell Stem Cell 13, 663–675 (2013).
Takashima, Y. et al. Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 158, 1254–1269 (2014).
Theunissen, T. W. et al. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 15, 471–487 (2014).
Ware, C. B. et al. Derivation of naive human embryonic stem cells. Proc. Natl Acad. Sci. USA 111, 4484–4489 (2014).
Chen, H. et al. Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency. Nat. Commun. 6, 7095 (2015).
Hanna, J. et al. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc. Natl Acad. Sci. USA 107, 9222–9227 (2010).
Pastor, W. A. et al. Naive human pluripotent cells feature a methylation landscape devoid of blastocyst or germline memory. Cell Stem Cell 18, 323–329 (2016).
Wang, J. et al. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. Nature 516, 405–409 (2014).
Guo, G. et al. Naive pluripotent stem cells derived directly from isolated cells of the human inner cell mass. Stem Cell Rep. 6, 437–446 (2016).
Duggal, G. et al. Alternative routes to induce naive pluripotency in human embryonic stem cells. Stem Cells 33, 2686–2698 (2015).
Carter, M. G. et al. A primitive growth factor, NME7AB, is sufficient to induce stable naive state human pluripotency; reprogramming in this novel growth factor confers superior differentiation. Stem Cells 34, 847–859 (2016).
Huang, K., Maruyama, T. & Fan, G. The naive state of human pluripotent stem cells: a synthesis of stem cell and preimplantation embryo transcriptome analyses. Cell Stem Cell 15, 410–415 (2014).
Chen, Y. et al. Generation of cynomolgus monkey chimeric fetuses using embryonic stem cells. Cell Stem Cell 17, 116–124 (2015).
Durruthy-Durruthy, J. et al. Spatiotemporal reconstruction of the human blastocyst by single-cell gene-expression analysis informs induction of naive pluripotency. Dev. Cell 38, 100–115 (2016).
Nakamura, T. et al. A developmental coordinate of pluripotency among mice, monkeys and humans. Nature 537, 57–62 (2016).
Morgani, S. M. et al. Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Rep. 3, 1945–1957 (2013).
Goke, J. et al. Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells. Cell Stem Cell 16, 135–141 (2015).
Hackett, J. A., Kobayashi, T., Dietmann, S. & Surani, M. A. Activation of lineage regulators and transposable elements across a pluripotent spectrum. Stem Cell Rep. 8, 1645–1658 (2017).
Beddington, R. S. & Robertson, E. J. An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development 105, 733–737 (1989).
Yang, J. et al. Establishment of mouse expanded potential stem cells. Nature 550, 393–397 (2017).
Yang, Y. et al. Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency. Cell 169, 243–257 (2017).
Mascetti, V. L. & Pedersen, R. A. Human-mouse chimerism validates human stem cell pluripotency. Cell Stem Cell 18, 67–72 (2016).
Wang, X. et al. Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis. Cell Res 28, 126–129 (2017).
Yang, Y. et al. Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure. Proc. Natl Acad. Sci. USA 112, 2337–2346 (2015).
Fenelon, J. C., Banerjee, A. & Murphy, B. D. Embryonic diapause: development on hold. Int. J. Dev. Biol. 58, 163–174 (2014).
Bulut-Karslioglu, A. et al. Inhibition of mTOR induces a paused pluripotent state. Nature 540, 119–123 (2016).
Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307–319 (2013).
Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376–380 (2012).
Li, M. et al. Efficient correction of hemoglobinopathy-causing mutations by homologous recombination in integration-free patient iPSCs. Cell Res. 21, 1740–1744 (2011).
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).
Suzuki, K. et al. In vivo genome editing via CRISPR-Cas9 mediated homology-independent targeted integration. Nature 540, 144–149 (2016).
Takahashi, Y. et al. Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells. Science 356, 503–508 (2017).
Flowers, G. P., Sanor, L. D. & Crews, C. M. Lineage tracing of genome-edited alleles reveals high fidelity axolotl limb regeneration. eLife 6, e25726 (2017).
McKenna, A. et al. Whole-organism lineage tracing by combinatorial and cumulative genome editing. Science 353, aaf7907 (2016).
Michlits, G. et al. CRISPR-UMI: single-cell lineage tracing of pooled CRISPR–Cas9 screens. Nat. Methods 14, 1191–1197 (2017).
Schroeder, T. Imaging stem-cell-driven regeneration in mammals. Nature 453, 345–351 (2008).
Lee, S. K., Mortensen, L. J., Lin, C. P. & Tung, C. H. An authentic imaging probe to track cell fate from beginning to end. Nat. Commun. 5, 5216 (2014).
Chen, B., Guan, J. & Huang, B. Imaging specific genomic DNA in living cells. Annu. Rev. Biophys. 45, 1–23 (2016).
Nelles, D. A. et al. Programmable RNA tracking in live cells with CRISPR/Cas9. Cell 165, 488–496 (2016).
Cahan, P. et al. CellNet: network biology applied to stem cell engineering. Cell 158, 903–915 (2014).
D’Alessio, A. C. et al. A systematic approach to identify candidate transcription factors that control cell identity. Stem Cell Rep. 5, 763–775 (2015).
Rackham, O. J. et al. A predictive computational framework for direct reprogramming between human cell types. Nat. Genet. 48, 331–335 (2016).
Ronquist, S. et al. Algorithm for cellular reprogramming. Proc. Natl Acad. Sci. USA 114, 11832–11837 (2017).
Wu, J. et al. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168, 473–486 (2017).
We apologize to the colleagues whose works are not covered due to space constraint. We would like to thank May Schwarz, Peter Schwarz, Chunmei Xia and Xingxing Zhang for generous administrative help during the preparation of the manuscript. We would like to thank the anonymous reviewers whose input has resulted in an improved manuscript. Work in the laboratory of M.L. was supported by King Abdullah University of Science and Technology (KAUST). Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002), the Moxie Foundation, NIH (5 DP1 DK113616 and R21AG055938), Progeria Research Foundation, Fundacion Dr. Pedro Guillen and the Universidad Católica San Antonio de Murcia (UCAM).
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Li, M., Izpisua Belmonte, J.C. Deconstructing the pluripotency gene regulatory network. Nat Cell Biol 20, 382–392 (2018). https://doi.org/10.1038/s41556-018-0067-6
Mutation Research/Reviews in Mutation Research (2020)
HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells
Nature Communications (2020)
SN Applied Sciences (2020)
Using Single-Cell and Spatial Transcriptomes to Understand Stem Cell Lineage Specification During Early Embryo Development
Annual Review of Genomics and Human Genetics (2020)
Developmental Biology (2020)