An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice.
An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice.
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DOI：
10.1016/j.stem.2017.03.023
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发表时间：
2017-07-06
期刊：
影响因子：
23.9
通讯作者：
Klein OD
中科院分区：
文献类型：
--
作者：
Hu JK;Du W;Shelton SJ;Oldham MC;DiPersio CM;Klein OD
Tissue homeostasis requires 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 α3 in TA cells that signals through a 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 proliferation of TA cells. These findings thus reveal a YAP/TAZ signaling mechanism that coordinates stem cell expansion and differentiation during organ renewal.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
10.5
作者：
Chen Q;Zhang N;Xie R;Wang W;Cai J;Choi KS;David KK;Huang B;Yabuta N;Nojima H;Anders RA;Pan D
通讯作者：
Pan D
影响因子：
3.8
作者：
Aggarwal, Anshu;Al-Rohil, Rami N.;DiPersio, C. Michael
通讯作者：
DiPersio, C. Michael
影响因子：
7.8
作者：
Harada, H;Kettunen, P;Jung, H S;Mustonen, T;Wang, Y A;Thesleff, I
通讯作者：
Thesleff, I
影响因子：
4.6
作者：
Klein, Ophir D.;Lyons, David B.;Balooch, Guive;Marshall, Grayson W.;Basson, M. Albert;Peterka, Miroslav;Boran, Tomas;Peterkova, Renata;Martin, Gail R.
通讯作者：
Martin, Gail R.