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Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF

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 Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing, conditional ablation, 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 Plzf lu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support a hierarchical model of a slow-cycling long-term SSC population supporting more rapid-cycling short-term SSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE116001 | GEO | 2019/05/30

REPOSITORIES: GEO

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