| First Author | Hu JK | Year | 2017 |
| Journal | Cell Stem Cell | Volume | 21 |
| Issue | 1 | Pages | 91-106.e6 |
| PubMed ID | 28457749 | Mgi Jnum | J:253651 |
| Mgi Id | MGI:6101349 | Doi | 10.1016/j.stem.2017.03.023 |
| Citation | Hu JK, et al. (2017) An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell 21(1):91-106.e6 |
| abstractText | Tissue homeostasis requires the production of newly differentiated cells from resident adult stem cells. Central to this process is the expansion of undifferentiated intermediates known as transit-amplifying (TA) cells, but how stem cells are triggered to enter this proliferative TA state remains an important open question. Using the continuously growing mouse incisor as a model of stem cell-based tissue renewal, we found that the transcriptional cofactors YAP and TAZ are required both to maintain TA cell proliferation and to inhibit differentiation. Specifically, we identified a pathway involving activation of integrin alpha3 in TA cells that signals through an LATS-independent FAK/CDC42/PP1A cascade to control YAP-S397 phosphorylation and nuclear localization. This leads to Rheb expression and potentiates mTOR signaling to drive the proliferation of TA cells. These findings thus reveal a YAP/TAZ signaling mechanism that coordinates stem cell expansion and differentiation during organ renewal. |
