Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases.
Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases.
复制标题
DOI：
10.1016/j.medj.2022.05.002
复制
发表时间：
2022-07-08
期刊：
影响因子：
17
通讯作者：
Raychaudhuri, Soumya
中科院分区：
文献类型：
--
作者：
Korsunsky, Ilya;Wei, Kevin;Pohin, Mathilde;Kim, Edy Y.;Barone, Francesca;Major, Triin;Taylor, Emily;Ravindran, Rahul;Kemble, Samuel;Watts, Gerald F. M.;Jonsson, A. Helena;Jeong, Yunju;Athar, Humra;Windell, Dylan;Kang, Joyce B.;Friedrich, Matthias;Turner, Jason;Nayar, Saba;Fisher, Benjamin A.;Raza, Karim;Marshall, Jennifer L.;Croft, Adam P.;Tamura, Tomoyoshi;Sholl, Lynette M.;Vivero, Marina;Rosas, Ivan O.;Bowman, Simon J.;Coles, Mark;Frei, Andreas P.;Lassen, Kara;Filer, Andrew;Powrie, Fiona;Buckley, Christopher D.;Brenner, Michael B.;Raychaudhuri, Soumya
促炎性成纤维细胞对于类风湿性关节炎、炎性肠病、间质性肺病和舍格伦综合征的发病机制至关重要，并且代表了慢性炎性疾病的新治疗靶点。然而，成纤维细胞表型的异质性，由于缺乏共同的跨组织分类学而加剧，限制了我们对多种疾病共享哪些途径的理解。我们用单细胞RNA测序分析了来自受影响个体的发炎和非发炎滑膜、肠、肺和唾液腺的成纤维细胞。我们将所有成纤维细胞整合到多组织图谱中，以表征共享和组织特异性表型。两个共有的簇，CXCL 10 + CCL 19+免疫相互作用和CXCL 10 + COL 3A 1+血管相互作用成纤维细胞，在所有发炎组织中扩增，并映射到公共特应性皮炎图谱中的真皮类似物。我们在肺、关节和肠道炎症的动物模型中证实了这些人促炎成纤维细胞。这项工作代表了对器官系统，个体供体和疾病状态的成纤维细胞的彻底调查，揭示了四种慢性炎症性疾病的共同致病激活状态。来自F. Hoffmann-La Roche（Roche）AG.成纤维细胞支持炎性疾病中的组织重组和免疫调节。Korsunsky等人构建了来自四种疾病（干燥综合征，间质性肺病，溃疡性结肠炎和类风湿性关节炎）的人成纤维细胞的单细胞图谱，定义了两种在疾病中共享的功能不同的炎性成纤维细胞表型，并确认了它们在独立数据集中的存在。
Pro-inflammatory fibroblasts are critical for pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren’s syndrome and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited our understanding of which pathways are shared by multiple diseases. We profiled fibroblasts derived from inflamed and non-inflamed synovium, intestine, lungs, and salivary glands from affected individuals with single-cell RNA sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes. Two shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts, were expanded in all inflamed tissues and mapped to dermal analogs in a public atopic dermatitis atlas. We confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation. This work represents a thorough investigation into fibroblasts across organ systems, individual donors, and disease states that reveals shared pathogenic activation states across four chronic inflammatory diseases. Grant from F. Hoffmann-La Roche (Roche) AG. Fibroblasts support tissue re-organization and immunoregulation in inflammatory diseases. Korsunsky et al. construct a single-cell atlas of human fibroblasts from four diseases (Sjögren’s syndrome, interstitial lung disease, ulcerative colitis, and rheumatoid arthritis), define two functionally distinct inflammatory fibroblast phenotypes shared across diseases, and confirm their presence in independent datasets.
登录
查看更多内容
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
17.1
作者：
Fonseka CY;Rao DA;Teslovich NC;Korsunsky I;Hannes SK;Slowikowski K;Gurish MF;Donlin LT;Lederer JA;Weinblatt ME;Massarotti EM;Coblyn JS;Helfgott SM;Todd DJ;Bykerk VP;Karlson EW;Ermann J;Lee YC;Brenner MB;Raychaudhuri S
通讯作者：
Raychaudhuri S
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
46.9
作者：
Bray, Nicolas L.;Pimentel, Harold;Pachter, Lior
通讯作者：
Pachter, Lior