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Publication : Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors.

First Author  Soliman H Year  2020
Journal  Cell Stem Cell Volume  26
Issue  2 Pages  205-220.e8
PubMed ID  31978365 Mgi Jnum  J:312032
Mgi Id  MGI:6713491 Doi  10.1016/j.stem.2019.12.008
Citation  Soliman H, et al. (2020) Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors. Cell Stem Cell 26(2):205-220.e8
abstractText  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.
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