Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids

Autor: João Pedro Alves-Lopes, Frederick C.K. Wong, Walfred W.C. Tang, Wolfram H. Gruhn, Navin B. Ramakrishna, Geraldine M. Jowett, Kirsi Jahnukainen, M. Azim Surani
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 1, Pp 111907- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2022.111907
Popis: Summary: Human primordial germ cells (hPGCs), the precursors of sperm and eggs, are specified during weeks 2−3 after fertilization. Few studies on ex vivo and in vitro cultured human embryos reported plausible hPGCs on embryonic day (E) 12−13 and in an E16−17 gastrulating embryo. In vitro, hPGC-like cells (hPGCLCs) can be specified from the intermediary pluripotent stage or peri-gastrulation precursors. Here, we explore the broad spectrum of hPGCLC precursors and how different precursors impact hPGCLC development. We show that resetting precursors can give rise to hPGCLCs (rhPGCLCs) in response to BMP. Strikingly, rhPGCLCs co-cultured with human hindgut organoids progress at a pace reminiscent of in vivo hPGC development, unlike those derived from peri-gastrulation precursors. Moreover, rhPGCLC specification depends on both EOMES and TBXT, not just on EOMES as for peri-gastrulation hPGCLCs. Importantly, our study provides the foundation for developing efficient in vitro models of human gametogenesis.
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