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研究解析人类肾脏纤维化中的成纤维细胞起源
2020-11-15 00:57

德国亚琛工业大学Rafael Kramann小组解析人类肾脏纤维化中的成纤维细胞起源。该项研究成果于2020年11月11日在线发表在《自然》杂志上。

研究人员使用单细胞RNA序列分析了健康和纤维化人类肾脏中近端肾小管和非近端肾小管细胞的转录组,从而以无偏倚方式绘制了整个人体肾脏。这使得研究人员能够以高分辨率对所有产生基质的细胞进行定位,从而揭示出周细胞和成纤维细胞的不同亚群,这是人类肾纤维化过程中形成成纤维细胞疤痕的主要来源。
 
研究人员在小鼠中使用了遗传谱系追踪、时序性单细胞RNA-seq和ATAC-seq实验以及人类肾脏纤维化中的空间转录组学来功能性地研究这些发现,为人类肾脏成肌纤维细胞以及它们的成纤维细胞和周细胞前体的起源、异质性和分化提供了新的思路。最后,研究人员使用这种策略来促进了靶标的发现,将Nkd2鉴定为人肾纤维化中成肌纤维细胞特异性靶标。
 
据介绍,肾脏纤维化是慢性肾脏疾病进展的标志,但是,目前还没有抗纤维化疗法。这主要是因为人们对人类肾脏纤维化过程中瘢痕形成细胞的起源、功能异质性和调节尚不清楚。
 
附:英文原文

Title: Decoding myofibroblast origins in human kidney fibrosis

Author: Christoph Kuppe, Mahmoud M. Ibrahim, Jennifer Kranz, Xiaoting Zhang, Susanne Ziegler, Javier Perales-Patn, Jitske Jansen, Katharina C. Reimer, James R. Smith, Ross Dobie, John R. Wilson-Kanamari, Maurice Halder, Yaoxian Xu, Nazanin Kabgani, Nadine Kaesler, Martin Klaus, Lukas Gernhold, Victor G. Puelles, Tobias B. Huber, Peter Boor, Sylvia Menzel, Remco M. Hoogenboezem, Eric M. J. Bindels, Joachim Steffens, Jrgen Floege, Rebekka K. Schneider, Julio Saez-Rodriguez, Neil C. Henderson, Rafael Kramann

Issue&Volume: 2020-11-11

Abstract: Kidney fibrosis is the hallmark of chronic kidney disease progression, however, currently no antifibrotic therapies exist.1–3 This is largely because the origin, functional heterogeneity and regulation of scar-forming cells during human kidney fibrosis remains poorly understood.1,2,4 Here, using single cell RNA-seq, we profiled the transcriptomes of proximal tubule and non-proximal tubule cells in healthy and fibrotic human kidneys to map the entire human kidney in an unbiased approach. This enabled mapping of all matrix-producing cells at high resolution, revealing distinct subpopulations of pericytes and fibroblasts as the major cellular sources of scar forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single cell RNA-seq and ATAC-seq experiments in mice, and spatial transcriptomics in human kidney fibrosis to functionally interrogate these findings, shedding new light on the origin, heterogeneity and differentiation of human kidney myofibroblasts and their fibroblast and pericyte precursors at unprecedented resolution. Finally, we used this strategy to facilitate target discovery, identifying Nkd2 as a myofibroblast-specific target in human kidney fibrosis.

DOI: 10.1038/s41586-020-2941-1

Source: https://www.nature.com/articles/s41586-020-2941-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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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