Brg1 is required for stem cell maintenance in the murine intestinal epithelium in a tissue-specific manner.
Brg1 is a chromatin remodeling factor involved in mediation of a plethora of signaling pathways leading to its participation in various physiological processes both during development and in adult tissues. Among other signaling pathways, the Wnt pathway has been proposed to require Brg1 for transactivation of its target genes. Given the pivotal role of the Wnt pathway in the maintenance of normal intestinal homeostasis, we aimed to investigate the effects of Brg1 loss on the intestinal physiology. To this end, we deleted Brg1 in the murine small and large intestinal epithelia using a range of transgenic approaches. Pan-epithelial loss of Brg1 in the small intestine resulted in crypt ablation, while partial Brg1 deficiency led to gradual repopulation of the intestinal mucosa with wild-type cells. In contrast, Brg1 loss in the large intestinal epithelium was compensated by upregulation of Brm. We propose that while Brg1 is dispensable for the survival and function of the progenitor and differentiated cells in the murine intestinal epithelium, it is essential for the maintenance of the stem cell population in a tissue-specific manner.
Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Aliaksei Z
AZ
Holik
Joanna
J
Krzystyniak
Madeleine
M
Young
Kirsty
K
Richardson
Thierry
T
Jardé
Pierre
P
Chambon
Boris Y
BY
Shorning
Alan R
AR
Clarke
D000818:Animals; D002454:Cell Differentiation; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
Brahma-related gene 1; Intestinal stem cell; SWItch/sucrose nonfermentable