First Author | Sharma M | Year | 2019 |
Journal | Elife | Volume | 8 |
PubMed ID | 31149899 | Mgi Jnum | J:276779 |
Mgi Id | MGI:6316687 | Doi | 10.7554/eLife.43352 |
Citation | Sharma M, et al. (2019) Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF. Elife 8:e43352 |
abstractText | 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. |