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bioRxiv · 10.1101/477604

Identification of slow-cycling germline stem cells and their regulation by PLZF

Braun, R. E.·Sharma, M.·Srivastava, A.·Fairfield, H. E.·Bergstrom, D.·Flynn, W. F.
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Abstract

Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf+/+ and Plzflu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES- GFRA1+ spermatogonia in wild-type but not in Plzflu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzflu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf+/+ and Plzflu/lu mice support a hierarchical model of both slow- and rapid-cycling SSCs.

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Braun, R. E., Sharma, M., Srivastava, A., Fairfield, H. E., Bergstrom, D., Flynn, W. F.. 2018-11-24. Identification of slow-cycling germline stem cells and their regulation by PLZF. https://doi.org/10.1101/477604

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