Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors.

Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors. Cell Stem Cell. 2020 Jan 20;: Authors: Soliman H, Paylor B, Scott RW, Lemos DR, Chang C, Arostegui M, Low M, Lee C, Fiore D, Braghetta P, Pospichalova V, Barkauskas CE, Korinek V, Rampazzo A, MacLeod K, Underhill TM, Rossi FMV Abstract 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. PMID: 31978365 [PubMed - as supplied by publishe...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research