Efficient generation of marmoset primordial germ cell-like cells using induced pluripotent stem cells

Yasunari Seita, Keren Cheng, John R. McCarrey, Nomesh Yadu, Ian Cheeseman, Alec Bagwell, Corinna N. Ross, Isamar Santana-Toro, Li Hua Yen, Sean Vargas, Christopher S. Navara, Brian P. Hermann, Kotaro Sasaki

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Reconstitution of germ cell fate from pluripotent stem cells provides an opportunity to understand the molecular underpinnings of germ cell development. Here, we established robust methods for pluripotent stem cell (iPSC) culture in the common marmoset (Callithrix jacchus, cj), allowing stable propagation in an undifferentiated state. Notably, iPSCs cultured on a feeder layer in the presence of a WNT signaling inhibitor upregulated genes related to ubiquitin-dependent protein catabolic processes and enter a permissive state that enables differentiation into primordial germ cell-like cells (PGCLCs) bearing immunophenotypic and transcriptomic similarities to pre-migratory cjPGCs in vivo. Induction of cjPGCLCs is accompanied by transient upregulation of mesodermal genes, culminating in the establishment of a primate specific germline transcriptional network. Moreover, cjPGCLCs can be expanded in monolayer while retaining the germline state. Upon co-culture with mouse testicular somatic cells, these cells acquire an early prospermatogonia-like phenotype. Our findings provide a framework for understanding and reconstituting marmoset germ cell development in vitro, thus providing a comparative tool and foundation for a preclinical modeling of human in vitro gametogenesis.

Original languageEnglish (US)
Article numbere82263
JournaleLife
Volume12
DOIs
StatePublished - Jan 2023

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience

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