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Cell Rep DOI:10.1016/j.celrep.2019.11.083

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

Publication TypeJournal Article
Year of Publication2019
AuthorsChen, D, Sun, N, Hou, L, Kim, R, Faith, J, Aslanyan, M, Tao, Y, Zheng, Y, Fu, J, Liu, W, Kellis, M, Clark, A
JournalCell Rep
Volume29
Issue13
Pages4568-4582.e5
Date Published2019 Dec 24
ISSN2211-1247
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.

DOI10.1016/j.celrep.2019.11.083
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31875561?dopt=Abstract

Alternate JournalCell Rep
PubMed ID31875561
PubMed Central IDPMC6939677
Grant ListR01 HD079546 / HD / NICHD NIH HHS / United States
R24 HD000836 / HD / NICHD NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States