小柯机器人

研究揭示不同组织中的成纤维细胞谱系
2021-05-16 15:59

近日,美国基因泰克公司Shannon. J. Turley等研究人员合作揭示不同组织中的成纤维细胞谱系。该研究于2021年5月12日在线发表于国际一流学术期刊《自然》。

通过整合来自17个组织、50个数据集、11个疾病状态和2个物种的大约230,000个成纤维细胞的单细胞转录组数据,研究人员构建了成纤维细胞图谱。小鼠成纤维细胞图谱和DptIRESCreERT2敲入小鼠在组织中鉴定出两种通用的成纤维细胞转录亚型。分析表明,这些细胞可以充当储存库,可以在疾病的广泛稳态组织和活化成纤维细胞中产生专门的成纤维细胞。与来自扰动状态的人类成纤维细胞图谱相比,小鼠和人类之间的成纤维细胞转录状态是保守的,包括通用的成纤维细胞和与人类癌症、纤维化、关节炎和炎症的致病性相关活化表型。总之,在单细胞分辨率下,不同物种和全组织的转录组学方法鉴定了健康和疾病中成纤维细胞谱系的关键组织原理。

据悉,成纤维细胞是非造血结构细胞,能够定义器官的结构,支持组织驻留细胞的稳态,并在纤维化、癌症、自身免疫和伤口愈合中起关键作用。最近的研究描述了单个组织内成纤维细胞的异质性。然而,该领域缺乏健康和患病器官中跨组织单细胞分辨率的成纤维细胞特征。

附:英文原文

Title: Cross-tissue organization of the fibroblast lineage

Author: Matthew B. Buechler, Rachana N. Pradhan, Akshay T. Krishnamurty, Christian Cox, Aslihan Karabacak Calviello, Amber W. Wang, Yeqing Angela Yang, Lucinda Tam, Roger Caothien, Merone Roose-Girma, Zora Modrusan, Joseph R. Arron, Richard Bourgon, Sren Mller, Shannon. J. Turley

Issue&Volume: 2021-05-12

Abstract: Fibroblasts are non-haematopoietic structural cells that define the architecture of organs, support the homeostasis of tissue-resident cells and have key roles in fibrosis, cancer, autoimmunity and wound healing1. Recent studies have described fibroblast heterogeneity within individual tissues1. However, the field lacks a characterization of fibroblasts at single-cell resolution across tissues in healthy and diseased organs. Here we constructed fibroblast atlases by integrating single-cell transcriptomic data from about 230,000 fibroblasts across 17 tissues, 50 datasets, 11 disease states and 2 species. Mouse fibroblast atlases and a DptIRESCreERT2 knock-in mouse identified two universal fibroblast transcriptional subtypes across tissues. Our analysis suggests that these cells can serve as a reservoir that can yield specialized fibroblasts across a broad range of steady-state tissues and activated fibroblasts in disease. Comparison to an atlas of human fibroblasts from perturbed states showed that fibroblast transcriptional states are conserved between mice and humans, including universal fibroblasts and activated phenotypes associated with pathogenicity in human cancer, fibrosis, arthritis and inflammation. In summary, a cross-species and pan-tissue approach to transcriptomics at single-cell resolution has identified key organizing principles of the fibroblast lineage in health and disease.

DOI: 10.1038/s41586-021-03549-5

Source: https://www.nature.com/articles/s41586-021-03549-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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