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 and busulfan challenge show that these are SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index in wild-type than in Plzf ^lu/lu mice, suggesting that PLZF regulates their proliferative activity and 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 the conclusion that SSCs are hierarchical yet heterogeneous.

SUBMITTER: Sharma M 

PROVIDER: S-EPMC6544432 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature