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). Overall design: 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.