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研究绘制出囊状纤维化气道的单细胞转录图谱
作者:小柯机器人 发布时间:2021/5/8 18:26:04

美国加州大学洛杉矶分校Brigitte N. Gomperts等研究人员合作绘制出囊状纤维化气道的单细胞转录图谱。相关论文于2021年5月6日在线发表在《自然—医学》杂志上。

研究人员表示,囊状纤维化(CF)是一种致命的常染色体隐性遗传疾病,影响了70,000多人。患有CF的人由于囊状纤维化跨膜电导调节因子(CFTR)基因的突变而经历了跨极化上皮的异常电解质运输,从而导致了多器官功能障碍。迄今为止,与CF相关的肺部疾病是发病率和死亡率的最重要决定因素。

研究人员报告了一个来自多机构联盟的结果:单细胞转录组学被用于通过比较接受终末期肺部疾病移植的CF供体(n=19)和先前健康的肺供体(n=19)的近端气道,从而确定与疾病相关的变化。观察到的疾病相关差异包括:上皮细胞过多转换为专门的纤毛和分泌细胞亚群,以及循环基底细胞的意外减少。这项研究产生了近端气道上皮的分子图谱,这将为开发针对CF气道疾病的新靶向疗法提供见识。

附:英文原文

Title: Transcriptional analysis of cystic fibrosis airways at single-cell resolution reveals altered epithelial cell states and composition

Author: Gianni Carraro, Justin Langerman, Shan Sabri, Zareeb Lorenzana, Arunima Purkayastha, Guangzhu Zhang, Bindu Konda, Cody J. Aros, Ben A. Calvert, Aleks Szymaniak, Emily Wilson, Michael Mulligan, Priyanka Bhatt, Junjie Lu, Preethi Vijayaraj, Changfu Yao, David W. Shia, Andrew J. Lund, Edo Israely, Tammy M. Rickabaugh, Jason Ernst, Martin Mense, Scott H. Randell, Eszter K. Vladar, Amy L. Ryan, Kathrin Plath, John E. Mahoney, Barry R. Stripp, Brigitte N. Gomperts

Issue&Volume: 2021-05-06

Abstract: Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality. Here we report results from a multi-institute consortium in which single-cell transcriptomics were applied to define disease-related changes by comparing the proximal airway of CF donors (n=19) undergoing transplantation for end-stage lung disease with that of previously healthy lung donors (n=19). Disease-dependent differences observed include an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subsets coupled with an unexpected decrease in cycling basal cells. Our study yields a molecular atlas of the proximal airway epithelium that will provide insights for the development of new targeted therapies for CF airway disease.

DOI: 10.1038/s41591-021-01332-7

Source: https://www.nature.com/articles/s41591-021-01332-7

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex