Lepr⁺ mesenchymal cells sense diet to modulate intestinal stem/progenitor cells via Leptin-Igf1 axis.

ABSTRACT: Diet can impact on gut health and disease by modulating intestinal stem cells (ISCs). However, it is largely unknown if and how the ISC niche responds to diet and influences ISC function. Here, we demonstrate that Lepr⁺ mesenchymal cells (MCs) surrounding intestinal crypts sense diet change and provide a novel niche signal to maintain ISC and progenitor cell proliferation. The abundance of these MCs increases upon administration of a high-fat diet (HFD) but dramatically decreases upon fasting. Depletion of Lepr⁺ MCs resulted in fewer intestinal stem/progenitor cells, compromised the architecture of crypt-villus axis and impaired intestinal regeneration. Furthermore, we showed that IGF1 secreted by Lepr⁺ MCs is an important effector that promotes proliferati

SUBMITTER: Deng M 

PROVIDER: S-EPMC9253134 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature