Transcription factor 21 regulates cardiac myofibroblast formation and fibrosis [scRNA-Seq]

Transcription factor 21 (TCF21) is a basic helix-loop-helix protein required for developmental specification of cardiac fibroblasts from epicardial progenitor cells that normally surround and invade the heart. In the adult heart, TCF21 is expressed in tissue-resident fibroblasts but is downregulated in response to injury or stimuli leading to myofibroblast differentiation. These findings led to the hypothesis that Tcf21 could be a regulator of fibroblast cell fate in the adult mammalian heart and contribute to cardiac fibrosis. Here, single-cell RNA-sequencing was used to study the effect of loss of Tcf21 in cardiac fibroblasts in adult mouse hearts at baseline and after an ischemic cardiac injury (myocardial infarction). To investigate the function of TCF21 in vivo, TCF21 was conditionally deleted in cardiac fibroblasts. Mice were either studied in the absense of injury or after 3 days of myocardial infarction. Cardiac tissue was digested to obtain a single cell suspension and live nucleated cells were sorted for single cell RNA sequencing.