Document Type

Article

Publication Date

5-31-2019

Keywords

JMG

JAX Source

eLife 2019; 8:e43352

PMID

31149899

DOI

https://doi.org/10.7554/eLife.43352

Grant

CA034196,HD042454

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.

Comments

We are extremely grateful to M Havrda and M Israel for providing us with Id4-/- mice, to D Krawchuk for her help in manuscript preparation and to The Single Cell Biology Lab at The Jackson Lab for Genomic Medicine.

Open access under the terms of the Creative Commons Attribution License

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