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  4. A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis

A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis

Journal Cell Reports 37(3):109875 (2021)
Title A multistate stem cell dynamics maintains homeostasis in mouse spermatogenesis.
Laboratory Laboratory of Stem Cell Biology and Developmental Immunology〈Prof. NAGASAWA Takashi〉
Abstract

In mouse testis, a heterogeneous population of undifferentiated spermatogonia (Aundiff) harbors spermatogenic stem cell (SSC) potential. Although GFRα1+ Aundiff maintains the self-renewing pool in homeostasis, the functional basis of heterogeneity and the implications for their dynamics remain unresolved. Here, through quantitative lineage tracing of SSC subpopulations, we show that an ensemble of heterogeneous states of SSCs supports homeostatic, persistent spermatogenesis. Such heterogeneity is maintained robustly through stochastic interconversion of SSCs between a renewal-biased Plvap+/GFRα1+ state and a differentiation-primed Sox3+/GFRα1+ state. In this framework, stem cell commitment occurs not directly but gradually through entry into licensed but uncommitted states. Further, Plvap+/GFRα1+ cells divide slowly, in synchrony with the seminiferous epithelial cycle, while Sox3+/GFRα1+ cells divide much faster. Such differential cell-cycle dynamics reduces mitotic load, and thereby the potential to acquire harmful de novo mutations of the self-renewing pool, while keeping the SSC density high over the testicular open niche.

Authors

Toshinori Nakagawa (1, 2, 3), David J. Jörg (4, 5), Hitomi Watanabe (6), Seiya Mizuno (7), Seungmin Han (4, 8), Tatsuro Ikeda (1), Yoshiki Omatsu (3, 9), Keiko Nishimura (1), Miyako Fujita (1), Satoru Takahashi (7, 10), Gen Kondoh (6), Benjamin D. Simons (4, 8, 11), Shosei Yoshida (1, 2), Takashi Nagasawa (3, 9)

  1. Division of Germ Cell Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan
  2. Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan
  3. Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
  4. The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
  5. Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK
  6. Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
  7. Laboratory Animal Resource Center and Trans-border Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  8. Wellcome Trust-Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 A0W, UK
  9. Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, World Premier International Immunology Frontier Research Center, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
  10. Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  11. Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA, UK
PubMed 34686326

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