Epiblast stem cell-based system reveals reprogramming synergy of germline factors

Astrid Gillich, Siqin Bao, Nils Grabole, Katsuhiko Hayashi, Matthew W.B. Trotter, Vincent Pasque, Erna Magnúsdóttir, M. Azim Surani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

Epigenetic reprogramming in early germ cells is critical toward the establishment of totipotency, but investigations of the germline events are intractable. An objective cell culture-based system could provide mechanistic insight on how the key determinants of primordial germ cells (PGCs), including Prdm14, induce reprogramming in germ cells to an epigenetic ground state. Here we show a Prdm14-Klf2 synergistic effect that can accelerate and enhance reversion of mouse epiblast stem cells (epiSCs) to a naive pluripotent state, including X reactivation and DNA demethylation. Notably, Prdm14 alone has little effect on epiSC reversion, but it enhances the competence for reprogramming and potentially PGC specification. Reprogramming of epiSCs by the combinatorial effect of Prdm14-Klf2 involves key epigenetic changes, which might have an analogous role in PGCs. Our study provides a paradigm toward a systematic analysis of how other key genes contribute to complex and dynamic events of reprogramming in the germline.

Original languageEnglish
Pages (from-to)425-439
Number of pages15
JournalCell Stem Cell
Volume10
Issue number4
DOIs
Publication statusPublished - 6 Apr 2012

Bibliographical note

Funding Information:
We thank Nigel Miller and Rachael Walker for flow cytometry, Julien Bauer and Charles Bradshaw for bioinformatics analysis, José Silva, Austin Smith, and Ge Guo for constructs, Toru Nakano and Huck-Hui Ng for antibodies, Joanna Wysocka for sharing unpublished data, and Harry Leitch and Katarzyna Wilczynska for comments on the manuscript. This work was supported by grants from the Wellcome Trust to A.G., N.G., V.P., and M.A.S. (RG44593, 081277).

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