한빛사논문
Meryem B. Baghdadi1,2, Arshad Ayyaz3, Sabrina Coquenlorge1,2, Bonnie Chu1,2, Sandeep Kumar3, Catherine Streutker4, Jeffrey L. Wrana2,3, Tae-Hee Kim1,2,5,*
1Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
2Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
3Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
4Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
5Lead contact
*Corresponding author
Abstract
The high turnover and regenerative capacity of the adult intestine relies on resident stem cells located at the bottom of the crypt. The enteric nervous system consists of an abundant network of enteric glial cells (EGCs) and neurons. Despite the close proximity of EGCs to stem cells, their in vivo role as a stem cell niche is still unclear. By analyzing the mouse and human intestinal mucosa transcriptomes at the single-cell level, we defined the regulation of EGC heterogeneity in homeostasis and chronic inflammatory bowel disease. Ablation of EGC subpopulations revealed that the repair potential of intestinal stem cells (ISCs) is regulated by a specific subset of glial fibrillary acidic protein (GFAP)+ EGCs. Mechanistically, injury induces expansion of GFAP+ EGCs, which express several WNT ligands to promote LGR5+ ISC self-renewal. Our work reveals the dynamically regulated heterogeneity of EGCs as a key part of the intestinal stem cell niche in regeneration and disease.
Keywords : Enteric glial cells, Intestinal stem cells, Stem cell niches, Regeneration, Inflammatory Bowel Disease, WNT signaling
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