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FBS Colloquia No.288Laboratory of Stem Cell Biology and Developmental Immunology

Seminar or Lecture

Mouse spermatogenic stem cells maintain homeostasis through the stochastic interconversion between undifferentiated and differentiation-primed states

Toshinori Nakagawa, PhD. [Assistant professor, Division of Germ Cell Biology,The National Institute for Basic Biology (NIBB)]

Date and Time 16 Dec. 2021 (Thu), 12:15~13:00
Place Online (Zoom) | An email will be sent with the meeting URL, ID, and password to all FBS members.
Language Japanese
Contact

Yoshiki Omatsu, Associate professor
E-mail: omatsu[at]fbs.osaka-u.ac.jp
TEL: EXT. 7968

Mouse spermatogenic stem cells maintain homeostasis through the stochastic interconversion between undifferentiated and differentiation-primed states

Spermatogenic stem cells (SSCs) are maintained in contact with their presumptive cellular niches, including sertoli cells and peritubular myoid cells in testis. Previous studies showed undifferentiated spermatogonia (Aundiff) contain SSCs in mouse testis by transplantation and regeneration assay. A decade ago, Nakagawa et al. showed that a subpopulation of Aundiff expressing GFRα1 includes steady-state stem cells in homeostasis (Nakagawa et al., Science 2010). However, the GFRα1+ population is still heterogeneous in their morphology and gene expression, and the identity of SSCs is under debate.
To reveal the function and nature of GFRα1+ subpopulations, we screened marker genes for SSCs, and identified two genes, including Plvap and Sox3. Plvap+/GFRα1+ and Sox3+/GFRα1+ cells exhibit immature and more mature morphology, respectively. Plvap+/GFRα1+ cells were enriched for SSCs. Through quantitative lineage tracing of GFRα1+ subpopulations, an ensemble of heterogeneous states of SSCs is observed during 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. Further, Plvap+/GFRα1+ cells divide slowly, while Sox3+/GFRα1+ cells divide much faster. Such differential dynamics may reduce mitotic load in SSCs and thereby the potential to acquire harmful de novo mutations in the self-renewing pool, while keeping many SSCs over the testicular open niche.

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