Developmental Cell
Volume 25, Issue 2, 29 April 2013, Pages 169-181
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Article
Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair

https://doi.org/10.1016/j.devcel.2013.03.015Get rights and content
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Highlights

  • Pathophysiological activation of Brg1 chromatin remodeler for tissue homeostasis

  • Maintenance of bulge stem cell reservoir by Brg1 chromatin remodeler

  • A positive Brg1-Shh tissue feedback loop governing hair follicle regeneration

Summary

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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