한빛사 논문
Seon Pyo Hong1,8, Myung Jin Yang2,8, Hyunsoo Cho1,3,8, Intae Park1, Hosung Bae1, Kibaek Choe4, Sang Heon Suh1,3, Ralf H. Adams5, Kari Alitalo6, Daesik Lim7 & Gou Young Koh1,2,3,*
1 Center for Vascular Research, Institute for Basic Science (IBS), Daejeon 34141, Republic of Korea.
2 Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
3 Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.
4 Graduate School of Nanoscience and Technology, KAIST, Daejeon 34141, Republic of Korea.
5 Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, and University of Münster, D-48149 Münster, Germany.
6 Translational Cancer Biology Program and Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, Helsinki 00290, Finland.
7 Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
8 These authors contributed equally: Seon Pyo Hong, Myung Jin Yang, Hyunsoo Cho.
*Corresponding author
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.
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TOP52020년 후보
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