TY - JOUR
T1 - Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair
AU - Xiong, Yiqin
AU - Li, Wei
AU - Shang, Ching
AU - Chen, Richard M.
AU - Han, Pei
AU - Yang, Jin
AU - Stankunas, Kryn
AU - Wu, Bingruo
AU - Pan, Minggui
AU - Zhou, Bin
AU - Longaker, Michael T.
AU - Chang, Ching Pin
N1 - Funding Information:
We thank G. Crabtree, A. Oro, P. Khavari, J. Chen, and J. Wu for discussions; S. Lyle for human bulge stem cells; M. Zhou for the IκB construct; P. Rack and J. Chen for Gli retroviral constructs; and P. Rack, S. Ko, J. Glotzbach, C. Hang, C.-Y.L., and C.-J. L. for advice. C.-P.C. was supported by funds from the California Institute of Regenerative Medicine (CIRM), National Institutes of Health (NIH), March of Dimes Foundation, American Heart Association (Established Investigator Award), and Oak Foundation. Y.X. was supported by fellowships from the Oak Foundation, Lucile Packard Foundation, and American Heart Association; C.S. by a Kirschstein-National Research Service Award Postdoctoral Fellowship; R.M.C. by the Oak Foundation; M.P. by the Kaiser Foundation; B.Z. by the NIH; and M.T.L. by the CIRM and Oak Foundation.
PY - 2013/4/29
Y1 - 2013/4/29
N2 - Hair follicle stem cells (bulge cells) are essential for hair regeneration and early epidermal repair after wounding. Here we show that Brg1, a key enzyme in the chromatin-remodeling machinery, is dynamically expressed in bulge cells to control tissue regeneration and repair. In mice, sonic hedgehog (Shh) signals Gli to activate Brg1 in bulge cells to begin hair regeneration, whereas Brg1 recruits NF-κB to activate Shh in matrix cells to sustain hair growth. Such reciprocal Brg1-Shh interaction is essential for hair regeneration. Moreover, Brg1 is indispensable for maintaining the bulge cell reservoir. Without Brg1, bulge cells are depleted over time, partly through the ectopic expression of the cell-cycle inhibitor p27Kip1. Also, bulge Brg1 is activated by skin injury to facilitate early epidermal repair. Our studies demonstrate a molecular circuit that integrates chromatin remodeling (Brg1), transcriptional regulation (NF-κB, Gli), and intercellular signaling (Shh) to control bulge stem cells during tissue regeneration.
AB - Hair follicle stem cells (bulge cells) are essential for hair regeneration and early epidermal repair after wounding. Here we show that Brg1, a key enzyme in the chromatin-remodeling machinery, is dynamically expressed in bulge cells to control tissue regeneration and repair. In mice, sonic hedgehog (Shh) signals Gli to activate Brg1 in bulge cells to begin hair regeneration, whereas Brg1 recruits NF-κB to activate Shh in matrix cells to sustain hair growth. Such reciprocal Brg1-Shh interaction is essential for hair regeneration. Moreover, Brg1 is indispensable for maintaining the bulge cell reservoir. Without Brg1, bulge cells are depleted over time, partly through the ectopic expression of the cell-cycle inhibitor p27Kip1. Also, bulge Brg1 is activated by skin injury to facilitate early epidermal repair. Our studies demonstrate a molecular circuit that integrates chromatin remodeling (Brg1), transcriptional regulation (NF-κB, Gli), and intercellular signaling (Shh) to control bulge stem cells during tissue regeneration.
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U2 - 10.1016/j.devcel.2013.03.015
DO - 10.1016/j.devcel.2013.03.015
M3 - Article
C2 - 23602386
AN - SCOPUS:84877001348
SN - 1534-5807
VL - 25
SP - 169
EP - 181
JO - Developmental Cell
JF - Developmental Cell
IS - 2
ER -