Direct cardiac reprogramming is a new technology which converts a somatic non-myocyte directly into an induced cardiomyocyte (iCM). This technology not only provides a promising platform for the study of cellular plasticity, disease modeling and drug screening, but also is considered a therapeutic approach capable of restoring the function of an injured heart. However, it still faces challenges in efficiently generating mature iCMs. Dr. Yang Zhou’s current research interests are to understand the molecular basis of direct cardiac reprogramming, with which to improve the clinical applicability and efficiency of this novel approach.
The cell fate of various cell types within an individual is determined and maintained mostly by distinct patterns of epigenetic modifications, which can help to determine whether genes are turned on or off. Cell reprogramming is inherently an epigenetic remodeling process. Zhou has identified a key epigenetic barrier to iCM reprogramming, as well as other epigenetic modifiers and splicing factors regulating reprogramming. Removal of these barriers largely enhance iCM reprogramming. Zhou has also determined the distinct molecular features between iCM and induced pluripotent stem cell-derived CMs (iPSC-CMs) through comparative transcriptomics and functional validations, providing guidance for future applications of each reprogramming approach. Her ongoing projects include development of efficient and reliable human iCM reprogramming platform, gene regulatory and epigenetic mechanisms underlying the direct cell fate conversion into human iCMs, and in situ heart regeneration via direct reprogramming.
