Enteric glial cell heterogeneity regulates intestinal stem cell niches

被引:79
作者
Baghdadi, Meryem B. [1 ,2 ]
Ayyaz, Arshad [3 ]
Coquenlorge, Sabrina [1 ,2 ]
Chu, Bonnie [1 ,2 ]
Kumar, Sandeep [3 ]
Streutker, Catherine [4 ]
Wrana, Jeffrey L. [2 ,3 ]
Kim, Tae-Hee [1 ,2 ]
机构
[1] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 0A4, Canada
[2] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
[3] Mt Sinai Hosp, Ctr Syst Biol, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada
[4] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada
基金
加拿大健康研究院;
关键词
SINGLE-CELL; NERVOUS-SYSTEM; EXPRESSION; INFLAMMATION; POPULATIONS; CATENIN; MARKER; PRECURSORS; MICROBIOTA; PLASTICITY;
D O I
10.1016/j.stem.2021.10.004
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:86 / +
页数:21
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