Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair

Yiqin Xiong, Wei Li, Ching Shang, Richard M. Chen, Pei Han, Jin Yang, Kryn Stankunas, Bingruo Wu, Minggui Pan, Bin Zhou, Michael T. Longaker, Ching Pin Chang

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)169-181
Number of pages13
JournalDevelopmental Cell
Volume25
Issue number2
DOIs
StatePublished - Apr 29 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair'. Together they form a unique fingerprint.

Cite this