| First Author | Hobbs RM | Year | 2010 |
| Journal | Cell | Volume | 142 |
| Issue | 3 | Pages | 468-79 |
| PubMed ID | 20691905 | Mgi Jnum | J:167931 |
| Mgi Id | MGI:4881375 | Doi | 10.1016/j.cell.2010.06.041 |
| Citation | Hobbs RM, et al. (2010) Plzf regulates germline progenitor self-renewal by opposing mTORC1. Cell 142(3):468-79 |
| abstractText | Hyperactivity of mTORC1, a key mediator of cell growth, leads to stem cell depletion, although the underlying mechanisms are poorly defined. Using spermatogonial progenitor cells (SPCs) as a model system, we show that mTORC1 impairs stem cell maintenance by a negative feedback from mTORC1 to receptors required to transduce niche-derived signals. We find that SPCs lacking Plzf, a transcription factor essential for SPC maintenance, have enhanced mTORC1 activity. Aberrant mTORC1 activation in Plzf(-/-) SPCs inhibits their response to GDNF, a growth factor critical for SPC self-renewal, via negative feedback at the level of the GDNF receptor. Plzf opposes mTORC1 activity by inducing expression of the mTORC1 inhibitor Redd1. Thus, we identify the mTORC1-Plzf functional interaction as a critical rheostat for maintenance of the spermatogonial pool and propose a model whereby negative feedback from mTORC1 to the GDNF receptor balances SPC growth with self-renewal. |
