Lymphatics and fibroblasts support intestinal stem cells in homeostasis and injury.

ABSTRACT: Lgr5⁺ intestinal stem cells (ISCs) depend on niche factors for their proper function. However, the source of these ISC niche factors and how they support ISCs in vivo remain controversial. Here, we report that ISCs depend on lymphatic endothelial cells (LECs) and RSPO3⁺GREM1⁺ fibroblasts (RGFs). In the intestine and colon, LECs are surrounded by RGFs and are located near ISCs at the crypt base. Both LECs and RGFs provide the critical ISC niche factor RSPO3 to support ISCs, where RSPO3 loss in both cell types drastically compromises ISC numbers, villi length, and repair after injury. In response to injury, LEC and RGF numbers expand and produce greater amounts of RSPO3 and other growth/angiocrine factors to foster intestinal repair. We propose that LECs repr

SUBMITTER: Goto N 

PROVIDER: S-EPMC9720889 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature