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。
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: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