Derivation of human primordial germ cell-like cells in an embryonic-like culture

Sajedeh Nasr Esfahani, Yi Zheng, Auriana Arabpour, Agnes M. Resto Irizarry, Norio Kobayashi, Xufeng Xue, Yue Shao, Cheng Zhao, Nicole L. Agranonik, Megan Sparrow, Timothy J. Hunt, Jared Faith, Mary Jasmine Lara, Qiu Ya Wu, Sherman Silber, Sophie Petropoulos, Ran Yang, Kenneth R. Chien, Amander T. Clark () and Jianping Fu ()
Additional contact information
Sajedeh Nasr Esfahani: University of Michigan
Yi Zheng: University of Michigan
Auriana Arabpour: University of California, Los Angeles
Agnes M. Resto Irizarry: University of Michigan
Norio Kobayashi: University of Michigan
Xufeng Xue: University of Michigan
Yue Shao: Tsinghua University
Cheng Zhao: Division of Obstetrics and Gynecology, Karolinska Instituet
Nicole L. Agranonik: University of California, Los Angeles
Megan Sparrow: University of California, Los Angeles
Timothy J. Hunt: University of California, Los Angeles
Jared Faith: University of California, Los Angeles
Mary Jasmine Lara: University of California, Los Angeles
Qiu Ya Wu: University of California, Los Angeles
Sherman Silber: Infertility Center of St. Louis, St. Luke’s Hospital
Sophie Petropoulos: Division of Obstetrics and Gynecology, Karolinska Instituet
Ran Yang: Karolinska Institutet
Kenneth R. Chien: Karolinska Institutet
Amander T. Clark: University of California, Los Angeles
Jianping Fu: University of Michigan

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution. Yet, hPGC specification remains an elusive process. Here, we report the induction of hPGC-like cells (hPGCLCs) in a bioengineered human pluripotent stem cell (hPSC) culture that mimics peri-implantation human development. In this culture, amniotic ectoderm-like cells (AMLCs), derived from hPSCs, induce hPGCLC specification from hPSCs through paracrine signaling downstream of ISL1. Our data further show functional roles of NODAL, WNT, and BMP signaling in hPGCLC induction. hPGCLCs are successfully derived from eight non-obstructive azoospermia (NOA) participant-derived hPSC lines using this biomimetic platform, demonstrating its promise for screening applications.

Date: 2024
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DOI: 10.1038/s41467-023-43871-2

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