Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF
| Autor: | Manju Sharma, Anuj Srivastava, Heather E Fairfield, David Bergstrom, William F Flynn, Robert E Braun |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | eLife, Vol 8 (2019) |
| Druh dokumentu: | article |
| ISSN: | 2050-084X 76764370 |
| DOI: | 10.7554/eLife.43352 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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