Exit from Naive Pluripotency Induces a Transient X Chromosome Inactivation-like State in Males

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 May 29

PMID 29804891

Citations 27

Authors

Elsa J Sousa

Hannah T Stuart

Lawrence E Bates

Mohammadmersad Ghorbani

Jennifer Nichols

Sabine Dietmann

Jose C R Silva

Affiliations

Soon will be listed here.

Abstract

A hallmark of naive pluripotency is the presence of two active X chromosomes in females. It is not clear whether prevention of X chromosome inactivation (XCI) is mediated by gene networks that preserve the naive state. Here, we show that robust naive pluripotent stem cell (nPSC) self-renewal represses expression of Xist, the master regulator of XCI. We found that nPSCs accumulate Xist on the male X chromosome and on both female X chromosomes as they become NANOG negative at the onset of differentiation. This is accompanied by the appearance of a repressive chromatin signature and partial X-linked gene silencing, suggesting a transient and rapid XCI-like state in male nPSCs. In the embryo, Xist is transiently expressed in males and in females from both X chromosomes at the onset of naive epiblast differentiation. In conclusion, we propose that XCI initiation is gender independent and triggered by destabilization of naive identity, suggesting that gender-specific mechanisms follow, rather than precede, XCI initiation.

Citing Articles

The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming.

Barrero M, Lazarenkov A, Blanco E, Palma L, Lopez-Rubio A, Bauer M Sci Adv. 2024; 10(32):eadj8862.

PMID: 39110794 PMC: 11305397. DOI: 10.1126/sciadv.adj8862.

Establishment and maintenance of random monoallelic expression.

Kanata E, Duffie R, Schulz E Development. 2024; 151(10).

PMID: 38813842 PMC: 11166465. DOI: 10.1242/dev.201741.

A Comparative Analysis of Mouse Imprinted and Random X-Chromosome Inactivation.

Malcore R, Kalantry S Epigenomes. 2024; 8(1).

PMID: 38390899 PMC: 10885068. DOI: 10.3390/epigenomes8010008.

Hallmarks of totipotent and pluripotent stem cell states.

Du P, Wu J Cell Stem Cell. 2024; 31(3):312-333.

PMID: 38382531 PMC: 10939785. DOI: 10.1016/j.stem.2024.01.009.

Three-dimensional genome structure and function.

Liu H, Tsai H, Yang M, Li G, Bian Q, Ding G MedComm (2020). 2023; 4(4):e326.

PMID: 37426677 PMC: 10329473. DOI: 10.1002/mco2.326.

References

Barakat T, Gunhanlar N, Pardo C, Achame E, Ghazvini M, Boers R . RNF12 activates Xist and is essential for X chromosome inactivation. PLoS Genet. 2011; 7(1):e1002001. PMC: 3029249. DOI: 10.1371/journal.pgen.1002001. View

Tian D, Sun S, Lee J . The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell. 2010; 143(3):390-403. PMC: 2994261. DOI: 10.1016/j.cell.2010.09.049. 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

Yagi M, Kishigami S, Tanaka A, Semi K, Mizutani E, Wakayama S . Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation. Nature. 2017; 548(7666):224-227. DOI: 10.1038/nature23286. View

Navarro P, Chambers I, Karwacki-Neisius V, Chureau C, Morey C, Rougeulle C . Molecular coupling of Xist regulation and pluripotency. Science. 2008; 321(5896):1693-5. DOI: 10.1126/science.1160952. View

Okamoto I, Otte A, Allis C, Reinberg D, Heard E . Epigenetic dynamics of imprinted X inactivation during early mouse development. Science. 2003; 303(5658):644-9. DOI: 10.1126/science.1092727. View

Beard C, Li E, Jaenisch R . Loss of methylation activates Xist in somatic but not in embryonic cells. Genes Dev. 1995; 9(19):2325-34. DOI: 10.1101/gad.9.19.2325. View

Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T . Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol. 2001; 11(19):1553-8. DOI: 10.1016/s0960-9822(01)00459-6. View

Mak W, Nesterova T, de Napoles M, Appanah R, Yamanaka S, Otte A . Reactivation of the paternal X chromosome in early mouse embryos. Science. 2004; 303(5658):666-9. DOI: 10.1126/science.1092674. View

10.

Navarro P, Moffat M, Mullin N, Chambers I . The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells. Hum Genet. 2011; 130(2):255-64. PMC: 3132432. DOI: 10.1007/s00439-011-0998-5. View

11.

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

12.

Sahakyan A, Kim R, Chronis C, Sabri S, Bonora G, Theunissen T . Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation. Cell Stem Cell. 2016; 20(1):87-101. PMC: 5218861. DOI: 10.1016/j.stem.2016.10.006. View

13.

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

14.

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

15.

Sanchez-Castillo M, Ruau D, Wilkinson A, Ng F, Hannah R, Diamanti E . CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities. Nucleic Acids Res. 2014; 43(Database issue):D1117-23. PMC: 4384009. DOI: 10.1093/nar/gku895. View

16.

Silva J, Mak W, Zvetkova I, Appanah R, Nesterova T, Webster Z . Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell. 2003; 4(4):481-95. DOI: 10.1016/s1534-5807(03)00068-6. View

17.

Silva J, Nichols J, Theunissen T, Guo G, van Oosten A, Barrandon O . Nanog is the gateway to the pluripotent ground state. Cell. 2009; 138(4):722-37. PMC: 3437554. DOI: 10.1016/j.cell.2009.07.039. View

18.

Xu N, Tsai C, Lee J . Transient homologous chromosome pairing marks the onset of X inactivation. Science. 2006; 311(5764):1149-52. DOI: 10.1126/science.1122984. View

19.

Chambers I, Silva J, Colby D, Nichols J, Nijmeijer B, Robertson M . Nanog safeguards pluripotency and mediates germline development. Nature. 2007; 450(7173):1230-4. DOI: 10.1038/nature06403. View

20.

Bacher C, Guggiari M, Brors B, Augui S, Clerc P, Avner P . Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nat Cell Biol. 2006; 8(3):293-9. DOI: 10.1038/ncb1365. View