Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Alves-Lopes, João Pedro 
Wong, Frederick CK 
Tang, Walfred WC 
Gruhn, Wolfram H 
Ramakrishna, Navin B 

Abstract

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.

Description

Keywords

CP: Stem cell research, Hindgut organoid, Primordial germ cell, Primordial germ cell-like cell precursor, Humans, Male, Semen, Cell Differentiation, Germ Cells, Embryo, Mammalian, Organoids

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (083089/Z/07/Z)
Wellcome Trust (209475/Z/17/Z)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (836291)
Medical Research Council (MR/P009948/1)
BBSRC (BB/T01346X/1)