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Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2020-01-20 , DOI: 10.1016/j.stem.2019.12.008 Hesham Soliman 1 , Ben Paylor 2 , R Wilder Scott 2 , Dario R Lemos 3 , ChihKai Chang 2 , Martin Arostegui 2 , Marcela Low 2 , Christina Lee 2 , Daniela Fiore 4 , Paola Braghetta 5 , Vendula Pospichalova 6 , Christina E Barkauskas 7 , Vladimir Korinek 6 , Alessandra Rampazzo 5 , Kathleen MacLeod 8 , T Michael Underhill 2 , Fabio M V Rossi 2
Cell Stem Cell ( IF 19.8 ) Pub Date : 2020-01-20 , DOI: 10.1016/j.stem.2019.12.008 Hesham Soliman 1 , Ben Paylor 2 , R Wilder Scott 2 , Dario R Lemos 3 , ChihKai Chang 2 , Martin Arostegui 2 , Marcela Low 2 , Christina Lee 2 , Daniela Fiore 4 , Paola Braghetta 5 , Vendula Pospichalova 6 , Christina E Barkauskas 7 , Vladimir Korinek 6 , Alessandra Rampazzo 5 , Kathleen MacLeod 8 , T Michael Underhill 2 , Fabio M V Rossi 2
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The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identified heart-resident PDGFRa+ SCA-1+ cells as cardiac fibro/adipogenic progenitors (cFAPs) and show that they respond to ischemic damage by generating fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (post-MI) remodeling and leads to improvement in cardiac function. In the undamaged heart, activation of cFAPs through lineage-specific deletion of the gene encoding the quiescence-associated factor HIC1 reveals additional pathogenic potential, causing fibrofatty infiltration within the myocardium and driving major pathological features pathognomonic in arrhythmogenic cardiomyopathy (AC). In this regard, cFAPs contribute to multiple pathogenic cell types within cardiac tissue and therapeutic strategies aimed at modifying their activity are expected to have tremendous benefit for the treatment of diverse cardiac diseases.
中文翻译：
表达Hic1的心脏基质干祖细胞的致病潜力。
心脏基质含有多能的间充质祖细胞。但是，心脏基质细胞内的血统关系定义不清。在这里，我们确定了驻留心脏的PDGFRa + SCA-1 +细胞为心脏纤维/脂肪生成祖细胞（cFAP），并显示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死后（MI）重塑，并改善心脏功能。在未受损的心脏中，通过谱系特异性删除编码静止相关因子HIC1的基因来激活cFAP揭示了更多的致病潜能，引起心肌内的纤维脂肪浸润，并驱动了心律失常性心肌病（AC）的主要病理特征。
更新日期：2020-01-23
中文翻译：
表达Hic1的心脏基质干祖细胞的致病潜力。
心脏基质含有多能的间充质祖细胞。但是，心脏基质细胞内的血统关系定义不清。在这里，我们确定了驻留心脏的PDGFRa + SCA-1 +细胞为心脏纤维/脂肪生成祖细胞（cFAP），并显示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死后（MI）重塑，并改善心脏功能。在未受损的心脏中，通过谱系特异性删除编码静止相关因子HIC1的基因来激活cFAP揭示了更多的致病潜能，引起心肌内的纤维脂肪浸润，并驱动了心律失常性心肌病（AC）的主要病理特征。
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