以色列魏兹曼科学研究所Ido Amit、Shuang-Yin Wang等研究人员合作发现，表达LGR5的皮肤成纤维细胞定义硬皮病中一个主要的细胞枢纽。相关论文发表在2022年4月14日出版的《细胞》杂志上。
Title: LGR5 expressing skin fibroblasts define a major cellular hub perturbed in scleroderma
Author: Chamutal Gur, Shuang-Yin Wang, Fadi Sheban, Mor Zada, Baoguo Li, Fadi Kharouf, Hagit Peleg, Suhail Aamar, Adam Yalin, Daniel Kirschenbaum, Yolanda Braun-Moscovici, Diego Adhemar Jaitin, Tomer meir-salame, Efrat Hagai, Bjrt K. Kragesteen, Batia Avni, Sigal Grisariu, Chamutal Bornstein, Shir Shlomi-Loubaton, Eyal David, Rony Shreberk-Hassidim, Vered Molho-Pessach, Dalit Amar, Tomer Tzur, Rottem Kuint, Moshe Gross, Oren Barboy, Adi Moshe, Liat Fellus-Alyagor, Dana Hirsch, Yoseph Addadi, Shlomit Erenfeld, Moshe Biton, Tehila Tzemach, Anat Elazary, Yaakov Naparstek, Reut Tzemach, Assaf Weiner, Amir Giladi, Alexandra Balbir-Gurman, Ido Amit
Issue&Volume: 2022/04/14
Abstract: Systemic sclerosis (scleroderma, SSc) is an incurable autoimmune disease with highmorbidity and mortality rates. Here, we conducted a population-scale single-cell genomicanalysis of skin and blood samples of 56 healthy controls and 97 SSc patients at differentstages of the disease. We found immune compartment dysfunction only in a specificsubtype of diffuse SSc patients but global dysregulation of the stromal compartment,particularly in a previously undefined subset of LGR5+-scleroderma-associated fibroblasts (ScAFs). ScAFs are perturbed morphologically andmolecularly in SSc patients. Single-cell multiome profiling of stromal cells revealedScAF-specific markers, pathways, regulatory elements, and transcription factors underliningdisease development. Systematic analysis of these molecular features with clinicalmetadata associates specific ScAF targets with disease pathogenesis and SSc clinicaltraits. Our high-resolution atlas of the sclerodermatous skin spectrum will enablea paradigm shift in the understanding of SSc disease and facilitate the developmentof biomarkers and therapeutic strategies.
DOI: 10.1016/j.cell.2022.03.011
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00314-2