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Publication : In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells.

First Author  Ishikura Y Year  2021
Journal  Cell Stem Cell Volume  28
Issue  12 Pages  2167-2179.e9
PubMed ID  34496297 Mgi Jnum  J:346849
Mgi Id  MGI:6874770 Doi  10.1016/j.stem.2021.08.005
Citation  Ishikura Y, et al. (2021) In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells. Cell Stem Cell 28(12):2167-2179.e9
abstractText  Mammalian male germ-cell development consists of three distinct phases: primordial germ cell (PGC) development, male germ-cell specification for spermatogonium development, and ensuing spermatogenesis. Here, we show an in vitro reconstitution of whole male germ-cell development by pluripotent stem cells (PSCs). Mouse embryonic stem cells (mESCs) are induced into PGC-like cells (mPGCLCs), which are expanded for epigenetic reprogramming. In reconstituted testes under an optimized condition, such mPGCLCs differentiate into spermatogonium-like cells with proper developmental transitions, gene expression, and cell-cycle dynamics and are expanded robustly as germline stem cell-like cells (GSCLCs) with an appropriate androgenetic epigenome. Importantly, GSCLCs show vigorous spermatogenesis, not only upon transplantation into testes in vivo but also under an in vitro culture of testis transplants, and the resultant spermatids contribute to fertile offspring. By uniting faithful recapitulations of the three phases of male germ-cell development, our study creates a paradigm for the in vitro male gametogenesis by PSCs.
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