Human Primordial Germ Cells Are Specified from Lineage-Primed Progenitors.

Cell Rep
Authors
Abstract

In vitro gametogenesis is the process of making germline cells from human pluripotent stem cells. The foundation of this model is the quality of the first progenitors called primordial germ cells (PGCs), which in vivo are specified during the peri-implantation window of human development. Here, we show that human PGC (hPGC) specification begins at day 12 post-fertilization. Using single-cell RNA sequencing of hPGC-like cells (hPGCLCs) differentiated from pluripotent stem cells, we discovered that hPGCLC specification involves resetting pluripotency toward a transitional state with shared characteristics between naive and primed pluripotency, followed by differentiation into lineage-primed TFAP2A progenitors. Applying the germline trajectory to TFAP2C mutants reveals that TFAP2C functions in the TFAP2A progenitors upstream of PRDM1 to regulate the expression of SOX17. This serves to protect hPGCLCs from crossing the Weismann's barrier to adopt somatic cell fates and, therefore, is an essential mechanism for successfully initiating in vitro gametogenesis.

Year of Publication
2019
Journal
Cell Rep
Volume
29
Issue
13
Pages
4568-4582.e5
Date Published
2019 Dec 24
ISSN
2211-1247
DOI
10.1016/j.celrep.2019.11.083
PubMed ID
31875561
PubMed Central ID
PMC6939677
Links
Grant list
R01 HD079546 / HD / NICHD NIH HHS / United States
R24 HD000836 / HD / NICHD NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States