Single cell RNA sequencing of Hic1 and PDGFRa-labeled cells in the heart. Single cell RNA sequencing of Hic1 and PDGFRa-labeled cells in the heart

The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identify heart-resident PDGFRa+ SCA-1+ cells as cardiac Fibro/Adipogenic Progenitors (cFAPs) and show that they respond to ischemic damage by generating SCA-1- fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (MI) remodeling and leads to improvement in heart function. Overall design: To understand the heterogeneity of cardiac mesenchymal progenitors in the heart, hearts were digested and cell suspensions of Hic1 CreERT2 tdTomato+, Hic1-citrine+ and PDGFRa H2BGFP+ cells were subjected to single cell RNA sequencing. Hic1 CreERT2 tdTomato+ and PDGFRa H2BGFP+ cells were collected from undamaged mice as well as 7 days after left anterior descending (LAD) coronary artery ligation. Hic1 citrine+ cells were only collected from undamaged mice. For the Hic1 CreERT2 tdTomato samples (for each time point), 3 mice hearts were pooled together in one sample. For the PDGFRa H2BGFP mice 4 mice hearts were hashed with anti-MHC I antibodies and pooled (2 undamaged and 2 7 days after LAD ligation). For the Hic1 citrine, cells from 3 undamaged hearts were hashed and pooled together and sequenced as 1 sample.