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Long‐term expansion with germline potential of human primordial germ cell‐like cells in vitro
Author(s) -
Murase Yusuke,
Yabuta Yukihiro,
Ohta Hiroshi,
Yamashiro Chika,
Nakamura Tomonori,
Yamamoto Takuya,
Saitou Mitinori
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020104929
Subject(s) - biology , germline , germ cell , microbiology and biotechnology , germ , in vitro , term (time) , genetics , gene , physics , quantum mechanics
Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell‐like cells ( hPGCLC s) derived from human‐induced pluripotent stem cells (hi PSC s) can be propagated to at least ~10 6 ‐fold over a period of 4 months under a defined condition in vitro . During expansion, hPGCLC s maintain an early hPGC ‐like transcriptome and preserve their genome‐wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLC s, which, under an analogous condition, show a limited propagation (up to ~50‐fold) and persist only around 1 week, yet undergo cell‐autonomous genome‐wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic‐reconstituted ovaries, expanded hPGCLC s initiate genome‐wide DNA demethylation and differentiate into oogonia/gonocyte‐like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.