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

Seon Pyo Hong; Myung Jin Yang; Hyunsoo Cho; Intae Park; Hosung Bae; Kibaek Choe; Sang Heon Suh; Ralf H Adams; Kari Alitalo; Daesik Lim; Gou Young Koh

doi:10.1038/s41467-020-17886-y

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

Journal article

Open access

Peer reviewed

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

Seon Pyo Hong, Myung Jin Yang, Hyunsoo Cho, Intae Park, Hosung Bae, Kibaek Choe, Sang Heon Suh, Ralf H Adams, Kari Alitalo, Daesik Lim, …

Nature communications, Vol.11(1), pp.4102-16

08/14/2020

DOI: 10.1038/s41467-020-17886-y

PMID: 32796823

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https://doi.org/10.1038/s41467-020-17886-yView

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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 PDGFRβ 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.

Acyltransferases

Adaptor Proteins, Signal Transducing - genetics

Adaptor Proteins, Signal Transducing - metabolism

Animals

Cell Cycle Proteins - genetics

Cell Cycle Proteins - metabolism

Cells, Cultured

Cluster Analysis

Enzyme-Linked Immunosorbent Assay

Fibroblasts - metabolism

Fibroblasts - ultrastructure

Flow Cytometry

Fluorescent Antibody Technique

In Situ Hybridization, Fluorescence

Intestinal Mucosa - metabolism

Intestinal Mucosa - ultrastructure

Lymphangiogenesis - genetics

Lymphangiogenesis - physiology

Mice

Mice, Inbred C57BL

Microscopy, Electron

Neovascularization, Physiologic - genetics

Neovascularization, Physiologic - physiology

Reverse Transcriptase Polymerase Chain Reaction

Transcription Factors - genetics

Transcription Factors - metabolism

Vascular Endothelial Growth Factor C - genetics

Vascular Endothelial Growth Factor C - metabolism

YAP-Signaling Proteins

Details

Title: Subtitle: Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi
Creators: Seon Pyo Hong - Institute for Basic Science
Myung Jin Yang - Korea Advanced Institute of Science and Technology
Hyunsoo Cho - Institute for Basic Science
Intae Park - Institute for Basic Science
Hosung Bae - Institute for Basic Science
Kibaek Choe - Korea Advanced Institute of Science and Technology
Sang Heon Suh - Korea Advanced Institute of Science and Technology
Ralf H Adams - University of Münster
Kari Alitalo - University of Helsinki
Daesik Lim - Department of Biological Sciences, KAIST, Daejeon, 34141, Republic of Korea
Gou Young Koh - Korea Advanced Institute of Science and Technology
Resource Type: Journal article
Publication Details: Nature communications, Vol.11(1), pp.4102-16
DOI: 10.1038/s41467-020-17886-y
PMID: 32796823
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Language: English
Date published: 08/14/2020
Academic Unit: Internal Medicine
Record Identifier: 9985217029102771

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