4.7 Article

Enteric glial cell heterogeneity regulates intestinal stem cell niches

Journal

CELL STEM CELL
Volume 29, Issue 1, Pages 86-+

Publisher

CELL PRESS
DOI: 10.1016/j.stem.2021.10.004

Keywords

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Funding

  1. SickKids Foundation start-up
  2. Canadian Institutes of Health Research (CIHR) [PJT 155923]
  3. March of Dimes Basil O'Connor Starter Scholar Research Award
  4. SickKids Restracomp postdoctoral fellowship
  5. CIHR foundation grant [FDN 143252]
  6. Terry Fox research grant
  7. CIHR

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This study investigates the heterogeneity and regulation of enteric glial cells (EGCs) in the intestine during homeostasis and chronic inflammatory bowel disease. A specific subset of glial cells, expressing GFAP, is found to regulate the repair potential of intestinal stem cells (ISCs) through the expression of WNT ligands. The dynamically regulated heterogeneity of EGCs is revealed to be a key part of the intestinal stem cell niche in regeneration and disease.
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.

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