Transcription Factor 21 Regulates Cardiac Myofibroblast Formation and Fibrosis | Circulation Research
BACKGROUND: TCF21 (transcription factor 21) is a bHLH (basic helix-loop-helix) protein required for the developmental specification of cardiac fibroblasts (CFs) from epicardial progenitor cells that surround the embryonic heart. In the adult heart, TCF21 is expressed in tissue-resident fibroblasts and is downregulated in response to injury or stimuli leading to myofibroblast differentiation. These findings led to the hypothesis that TCF21 regulates fibroblast differentiation in the adult mammalian heart to affect fibrosis. METHODS: Tamoxifen-inducible Cre genetic mouse models were used to permit either Tcf21 gene deletion or its enforced expression in adult CFs. Histological and echocardiographic analyses were used, as well as transcriptomic analysis to determine the consequences of TCF21 gain-of-function and loss-of-function in vivo. Genomic Tcf21 occupancy was identified by chromatin immunoprecipitation and sequencing in CFs. Myocardial infarction and AngII (angiotensin II)/phenyleph
