TY - JOUR
T1 - Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells
AU - Hayashi, Katsuhiko
AU - Ohta, Hiroshi
AU - Kurimoto, Kazuki
AU - Aramaki, Shinya
AU - Saitou, Mitinori
N1 - Funding Information:
We thank J. Nichols for her advice on the ground state ESC culture. We are grateful to K. Okita and S. Yamanaka for the information on germline transmission of the three iPSC lines. We also thank K. Kabashima, H. Tanizaki, K. Takakura, S. Chuma, and N. Nakatsuji for their support with the FACS analysis; A. Fukunaga for her help with bisulfate sequence analysis; and Y. Toda for his help with the histology. S.A. is a JSPS research fellow. This study was supported, in part, by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; by JST-CREST; by the Takeda Science Foundation; and by the Uehara Memorial Foundation.
PY - 2011/8/19
Y1 - 2011/8/19
N2 - The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-β3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.
AB - The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-β3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.
UR - http://www.scopus.com/inward/record.url?scp=80052022935&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052022935&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2011.06.052
DO - 10.1016/j.cell.2011.06.052
M3 - Article
C2 - 21820164
AN - SCOPUS:80052022935
SN - 0092-8674
VL - 146
SP - 519
EP - 532
JO - Cell
JF - Cell
IS - 4
ER -