Tracking the Embryonic Stem Cell Transition from Ground State Pluripotency

Overview

Journal Development

Specialty Biology

Date 2017 Feb 9

PMID 28174249

Citations 148

Authors

Tuzer Kalkan

Nelly Olova

Mila Roode

Carla Mulas

Heather J Lee

Isabelle Nett

Hendrik Marks

Rachael Walker

Hendrik G Stunnenberg

Kathryn S Lilley

Jennifer Nichols

Wolf Reik

Paul Bertone

Austin Smith

Affiliations

Soon will be listed here.

Abstract

Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naïve pluripotency. Here, we examine the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life reporter to isolate cells either side of exit from naïve status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state display features of early post-implantation epiblast and are distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naïve cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.

Citing Articles

A stepwise mode of TGFβ-SMAD signaling and DNA methylation regulates naïve-to-primed pluripotency and differentiation.

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Lineage-specific CDK activity dynamics characterize early mammalian development.

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Early human development and stem cell-based human embryo models.

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A suboptimal OCT4-SOX2 binding site facilitates the naïve-state specific function of a Klf4 enhancer.

Waite J, Boytz R, Traeger A, Lind T, Lumbao-Conradson K, Torigoe S PLoS One. 2024; 19(9):e0311120.

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References

Heintzman N, Stuart R, Hon G, Fu Y, Ching C, Hawkins R . Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007; 39(3):311-8. DOI: 10.1038/ng1966. View

Yang S, Kalkan T, Morissroe C, Marks H, Stunnenberg H, Smith A . Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency. Cell Rep. 2014; 7(6):1968-81. PMC: 4074343. DOI: 10.1016/j.celrep.2014.05.037. View

Habibi E, Brinkman A, Arand J, Kroeze L, Kerstens H, Matarese F . Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell. 2013; 13(3):360-9. DOI: 10.1016/j.stem.2013.06.002. View

Hnisz D, Abraham B, Lee T, Lau A, Saint-Andre V, Sigova A . Super-enhancers in the control of cell identity and disease. Cell. 2013; 155(4):934-47. PMC: 3841062. DOI: 10.1016/j.cell.2013.09.053. View

Leeb M, Dietmann S, Paramor M, Niwa H, Smith A . Genetic exploration of the exit from self-renewal using haploid embryonic stem cells. Cell Stem Cell. 2014; 14(3):385-93. PMC: 3995090. DOI: 10.1016/j.stem.2013.12.008. View

Takashima Y, Guo G, Loos R, Nichols J, Ficz G, Krueger F . Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell. 2014; 158(6):1254-1269. PMC: 4162745. DOI: 10.1016/j.cell.2014.08.029. View

Zhang J, Ratanasirintrawoot S, Chandrasekaran S, Wu Z, Ficarro S, Yu C . LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency. Cell Stem Cell. 2016; 19(1):66-80. DOI: 10.1016/j.stem.2016.05.009. View

Respuela P, Nikolic M, Tan M, Frommolt P, Zhao Y, Wysocka J . Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification. Cell Stem Cell. 2016; 18(1):118-33. PMC: 5048917. DOI: 10.1016/j.stem.2015.09.010. View

Blow M, McCulley D, Li Z, Zhang T, Akiyama J, Holt A . ChIP-Seq identification of weakly conserved heart enhancers. Nat Genet. 2010; 42(9):806-10. PMC: 3138496. DOI: 10.1038/ng.650. View

10.

Leitch H, McEwen K, Turp A, Encheva V, Carroll T, Grabole N . Naive pluripotency is associated with global DNA hypomethylation. Nat Struct Mol Biol. 2013; 20(3):311-6. PMC: 3591483. DOI: 10.1038/nsmb.2510. View

11.

Liu P, Dou X, Liu C, Wang L, Xing C, Peng G . Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate. Nat Commun. 2015; 6:6830. DOI: 10.1038/ncomms7830. View

12.

Zhang X, Yu H, Wang F, Han Y, Yang W . Pim-2 Modulates Aerobic Glycolysis and Energy Production during the Development of Colorectal Tumors. Int J Med Sci. 2015; 12(6):487-93. PMC: 4466513. DOI: 10.7150/ijms.10982. View

13.

Toyooka Y, Shimosato D, Murakami K, Takahashi K, Niwa H . Identification and characterization of subpopulations in undifferentiated ES cell culture. Development. 2008; 135(5):909-18. DOI: 10.1242/dev.017400. View

14.

Alexandrova S, Kalkan T, Humphreys P, Riddell A, Scognamiglio R, Trumpp A . Selection and dynamics of embryonic stem cell integration into early mouse embryos. Development. 2015; 143(1):24-34. PMC: 4725202. DOI: 10.1242/dev.124602. View

15.

Kim J, Chu J, Shen X, Wang J, Orkin S . An extended transcriptional network for pluripotency of embryonic stem cells. Cell. 2008; 132(6):1049-61. PMC: 3837340. DOI: 10.1016/j.cell.2008.02.039. View

16.

Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H . The transcriptional and epigenomic foundations of ground state pluripotency. Cell. 2012; 149(3):590-604. PMC: 3398752. DOI: 10.1016/j.cell.2012.03.026. View

17.

Kalkan T, Smith A . Mapping the route from naive pluripotency to lineage specification. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1657). PMC: 4216463. DOI: 10.1098/rstb.2013.0540. View

18.

Chen X, Xu H, Yuan P, Fang F, Huss M, Vega V . Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell. 2008; 133(6):1106-17. DOI: 10.1016/j.cell.2008.04.043. View

19.

Murphy L, MacKeigan J, Blenis J . A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration. Mol Cell Biol. 2003; 24(1):144-53. PMC: 303364. DOI: 10.1128/MCB.24.1.144-153.2004. View

20.

Ohinata Y, Ohta H, Shigeta M, Yamanaka K, Wakayama T, Saitou M . A signaling principle for the specification of the germ cell lineage in mice. Cell. 2009; 137(3):571-84. DOI: 10.1016/j.cell.2009.03.014. View