Premium
Gata6 promotes hair follicle progenitor cell renewal by genome maintenance during proliferation
Author(s) -
Wang Alex B,
Zhang Ying V,
Tumbar Tudorita
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694572
Subject(s) - biology , progenitor , hair follicle , progenitor cell , microbiology and biotechnology , genome , stem cell , cell growth , genetics , computational biology , gene
Abstract Cell proliferation is essential to rapid tissue growth and repair, but can result in replication‐associated genome damage. Here, we implicate the transcription factor Gata6 in adult mouse hair follicle regeneration where it controls the renewal of rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that in vivo Gata6 stimulates EDA ‐receptor signaling adaptor Edaradd level and NF ‐κB pathway activation, known to be important for DNA damage repair and stress response in general and for hair follicle growth in particular. In cultured keratinocytes, Edaradd rescues DNA damage, cell survival, and proliferation of Gata6 knockout cells and restores MCM 10 expression. Our data add to recent evidence in embryonic stem and neural progenitor cells, suggesting a model whereby developmentally regulated transcription factors protect from DNA damage associated with proliferation at key stages of rapid tissue growth. Our data may add to understanding why Gata6 is a frequent target of amplification in cancers.