TY - JOUR
T1 - Generation of human oogonia from induced pluripotent stem cells in vitro
AU - Yamashiro, Chika
AU - Sasaki, Kotaro
AU - Yabuta, Yukihiro
AU - Kojima, Yoji
AU - Nakamura, Tomonori
AU - Okamoto, Ikuhiro
AU - Yokobayashi, Shihori
AU - Murase, Yusuke
AU - Ishikura, Yukiko
AU - Shirane, Kenjiro
AU - Sasaki, Hiroyuki
AU - Yamamoto, Takuya
AU - Saitou, Mitinori
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Specially Promoted Research from the Japan Society for the Promotion of Science (JSPS) (17H06098) to M.S., by a JST-ERATO grant (JPMJER1104) to M.S., by funds from the HEALIOS to K.K. and the Pythias Fund to M.S., and by a Grant-in-Aid for Scientific Research on Innovative Areas and Specially Promoted Research from JSPS to H.S. (25112010 and 18H05214).
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/10/19
Y1 - 2018/10/19
N2 - Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells.The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs-and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.
AB - Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells.The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs-and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.
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U2 - 10.1126/science.aat1674
DO - 10.1126/science.aat1674
M3 - Article
C2 - 30237246
AN - SCOPUS:85055195876
SN - 0036-8075
VL - 362
SP - 356
EP - 360
JO - Science
JF - Science
IS - 6412
ER -
