کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2036208 | 1072249 | 2010 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Plzf Regulates Germline Progenitor Self-Renewal by Opposing mTORC1 Plzf Regulates Germline Progenitor Self-Renewal by Opposing mTORC1](/preview/png/2036208.png)
SummaryHyperactivity 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.
Graphical AbstractFigure optionsDownload high-quality image (209 K)Download as PowerPoint slideHighlights
► Plzf maintains the undifferentiated state of spermatogonial progenitor cells (SPCs)
► Plzf inhibits activity of the mTORC1 pathway in SPCs by inducing Redd1
► Increased mTORC1 activity inhibits response of SPCs to the niche-derived factor GDNF
► Inhibiting mTORC1 attenuates Plzf−/− SPC defects and enhances wild-type SPC activity
Journal: - Volume 142, Issue 3, 6 August 2010, Pages 468–479