Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells

Young Sun Hwang, Shinnosuke Suzuki, Yasunari Seita, Jumpei Ito, Yuka Sakata, Hirofumi Aso, Kei Sato, Brian P. Hermann and Kotaro Sasaki ()
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Young Sun Hwang: University of Pennsylvania Perelman School of Medicine
Shinnosuke Suzuki: University of Texas at San Antonio
Yasunari Seita: University of Pennsylvania Perelman School of Medicine
Jumpei Ito: The University of Tokyo
Yuka Sakata: University of Pennsylvania Perelman School of Medicine
Hirofumi Aso: The University of Tokyo
Kei Sato: The University of Tokyo
Brian P. Hermann: University of Texas at San Antonio
Kotaro Sasaki: University of Pennsylvania Perelman School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Establishment of spermatogonia throughout the fetal and postnatal period is essential for production of spermatozoa and male fertility. Here, we establish a protocol for in vitro reconstitution of human prospermatogonial specification whereby human primordial germ cell (PGC)-like cells differentiated from human induced pluripotent stem cells are further induced into M-prospermatogonia-like cells and T1 prospermatogonia-like cells (T1LCs) using long-term cultured xenogeneic reconstituted testes. Single cell RNA-sequencing is used to delineate the lineage trajectory leading to T1LCs, which closely resemble human T1-prospermatogonia in vivo and exhibit gene expression related to spermatogenesis and diminished proliferation, a hallmark of quiescent T1 prospermatogonia. Notably, this system enables us to visualize the dynamic and stage-specific regulation of transposable elements during human prospermatogonial specification. Together, our findings pave the way for understanding and reconstructing human male germline development in vitro.

Date: 2020
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DOI: 10.1038/s41467-020-19350-3

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