Identification of a multi-potent Twist2-expressing cell population in the adult heart (RNA-seq data set). Mus musculus

Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from Drosophlia to mammals. Through lineage tracing of Twist2 (Tw2) expressing cells with tamoxifen-inducible Tw2-CreERT2 and tdTomato reporter mice, we discovered a unique cell population that progressively contributes to multiple cell types in the adult heart, including cardiomyocytes, endothelial cells and fibroblasts. Clonal analysis confirmed the ability of Tw2-derived tdTO+ (Tw2-tdTO+) cells to form CMs in vitro. Within the adult heart, Tw2-tdTO+ cardiomyocytes accounted for ~13% of total cardiomyocytes, the majority of which resulted from fusion of Tw2-tdTO+ cells with existing cardiomyocytes. Tw2-tdTO+ cells also contribute to cardiac remodeling after injury. We conclude that a Tw2-tdTO+ cells participate in lifelong maintenance of cardiac function, at least in part through de novo formation of cardiomyocytes and fusion with preexisting cardiomyocytes, as well as in the genesis of other cellular components of the adult heart. Overall design: For RNA-seq dataset, gene expression profile was generated comparing Tw2- and Tw2+ non-CMs in the heart, by deep seqencing, with three biological replicates, using Illumina HiSeq 2500. For single cell RNA-seq dataset, gene expression profile was generated using 10x genomics platform with four biological replicates, using illumina Nextseq 500.