Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi

Show full item record



Permalink

http://hdl.handle.net/10138/319661

Citation

Hong , S P , Yang , M J , Cho , H , Park , I , Bae , H , Choe , K , Suh , S H , Adams , R H , Alitalo , K , Lim , D & Koh , G Y 2020 , ' Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi ' , Nature Communications , vol. 11 , no. 1 , 4102 . https://doi.org/10.1038/s41467-020-17886-y

Title: Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi
Author: Hong, Seon Pyo; Yang, Myung Jin; Cho, Hyunsoo; Park, Intae; Bae, Hosung; Choe, Kibaek; Suh, Sang Heon; Adams, Ralf H.; Alitalo, Kari; Lim, Daesik; Koh, Gou Young
Contributor: University of Helsinki, HUSLAB
Date: 2020-08-14
Language: eng
Number of pages: 16
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/319661
Abstract: Emerging evidence suggests that intestinal stromal cells (IntSCs) play essential roles in maintaining intestinal homeostasis. However, the extent of heterogeneity within the villi stromal compartment and how IntSCs regulate the structure and function of specialized intestinal lymphatic capillary called lacteal remain elusive. Here we show that selective hyperactivation or depletion of YAP/TAZ in PDGFR beta(+) IntSCs leads to lacteal sprouting or regression with junctional disintegration and impaired dietary fat uptake. Indeed, mechanical or osmotic stress regulates IntSC secretion of VEGF-C mediated by YAP/TAZ. Single-cell RNA sequencing delineated novel subtypes of villi fibroblasts that upregulate Vegfc upon YAP/TAZ activation. These populations of fibroblasts were distributed in proximity to lacteal, suggesting that they constitute a peri-lacteal microenvironment. Our findings demonstrate the heterogeneity of IntSCs and reveal that distinct subsets of villi fibroblasts regulate lacteal integrity through YAP/TAZ-induced VEGF-C secretion, providing new insights into the dynamic regulatory mechanisms behind lymphangiogenesis and lymphatic remodeling.
Subject: HIPPO PATHWAY
CARDIOMYOCYTE PROLIFERATION
LYMPHATIC VASCULATURE
YAP
CELLS
REGENERATION
MECHANISMS
GROWTH
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41467_020_17886_y.pdf 8.439Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record