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表达Hic1的心脏基质祖细胞具有致病潜力
作者:小柯机器人 发布时间:2020/2/4 15:24:01

加拿大英属哥伦比亚大学Fabio M.V. Rossi研究团队揭示了表达Hic1的心脏基质祖细胞的致病潜力。2020年1月23日,国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员确定了驻留于心脏的PDGFRa+SCA-1+细胞为心脏纤维/脂肪生成祖细胞(cFAP),并发现它们通过产生纤维生成细胞对缺血性损伤做出反应。用抗纤维化酪氨酸激酶抑制剂对该分化步骤进行药理学阻断可减少心肌梗塞后(MI)重塑并改善心脏功能。在未受损的心脏中,通过谱系特异性敲除编码静止相关因子HIC1的基因能够激活cFAP,从而揭示了更多的致病潜能,并引起心肌内纤维脂肪浸润,从而产生了心律失常性心肌病(AC)的主要病理特征。因此,cFAP有助于心脏组织内的多种致病细胞类型,而旨在改善其活性的治疗策略有望对多种心脏疾病治疗产生巨大益处。
 
据悉,心脏基质含有多能的间充质祖细胞。但是,心脏基质细胞的谱系关系定义不清。
 
附:英文原文

Title: Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors

Author: Hesham Soliman, Ben Paylor, R. Wilder Scott, Dario R. Lemos, ChihKai Chang, Martin Arostegui, Marcela Low, Christina Lee, Daniela Fiore, Paola Braghetta, Vendula Pospichalova, Christina E. Barkauskas, Vladimir Korinek, Alessandra Rampazzo, Kathleen MacLeod, T. Michael Underhill, Fabio M.V. Rossi

Issue&Volume: January 23, 2020

Abstract: The cardiac stroma contains multipotent mesenchymal progenitors. However, lineagerelationships within cardiac stromal cells are poorly defined. Here, we identifiedheart-resident PDGFRa+ SCA-1+ cells as cardiac fibro/adipogenic progenitors (cFAPs) and show that they respondto ischemic damage by generating fibrogenic cells. Pharmacological blockade of thisdifferentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardialinfarction (post-MI) remodeling and leads to improvement in cardiac function. In theundamaged heart, activation of cFAPs through lineage-specific deletion of the geneencoding the quiescence-associated factor HIC1 reveals additional pathogenic potential,causing fibrofatty infiltration within the myocardium and driving major pathologicalfeatures pathognomonic in arrhythmogenic cardiomyopathy (AC). In this regard, cFAPscontribute to multiple pathogenic cell types within cardiac tissue and therapeuticstrategies aimed at modifying their activity are expected to have tremendous benefitfor the treatment of diverse cardiac diseases.

DOI: 10.1016/j.stem.2019.12.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30526-0

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx