Human Primordial Germ Cells Are Specified from Lineage-Primed Progenitors
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1-s2.0-S2211124719315748-main.pdf
Description
Published version
Size
6.47 MB
Format
Adobe PDF
Checksum (MD5)
8307a1ae9836914a9a221ea94b6c2997
Author(s)
Chen, Di
Sun, Na
Hou, Lei
Kim, Rachel
Faith, Jared
Aslanyan, Marianna
Tao, Yu
Zheng, Yi
Fu, Jianping
Liu, Wanlu
Date Issued
December 2019
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Chen, Di et al. "Human Primordial Germ Cells Are Specified from Lineage-Primed Progenitors." Cell Reports 29, 13 (December 2019): P4568-4582.e5 © 2019 The Author(s)
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2019.11.083
