biostudies-literatureMin YLHHS | National Institutes of HealthAmerican Heart AssociationFondation LeducqNHLBI NIH HHSWelch FoundationNIAMS NIH HHSCancer Prevention and Research Institute of TexasNIH HHSE8430-E8439https://www.ebi.ac.uk/biostudies/studies/S-EPMC6130356biostudies-literatureUnknown115(36)Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from <i>Drosophila</i> to mammals. Through lineage tracing of Twist2 (Tw2)-expressing cells with tamoxifen-inducible Tw2-CreERT2 and tdTomato (tdTO) reporter mice, we discovered a unique cell population that progressively contributes to cardiomyocytes (CMs), endothelial cells, and fibroblasts in the adult heart. Clonal analysis confirmed the ability of Tw2-derived tdTO⁺ (Tw2-tdTO⁺) cells to form CMs in vitro. Within the adult heart, Tw2-tdTO⁺ CMs accounted for ∼13% of total CMs, the majority of which resulted from fusion of Tw2-tdTO⁺ cells with existing CMs. Tw2-tdTO⁺ cells also contribute to cardiac remodeling after injury. We coProceedings of the National Academy of Sciences of the United States of AmericaIdentification of a multipotent Twist2-expressing cell population in the adult heart.PMC61303561-0025R01 AR067294R01 AR071980RP15059613BGIA17150004R01 HL130253HL-130253HL-138426 and AR-071980S10 OD018005R01 HL138426AR-067294Transatlantic Networks of Excellence in Cardiovascular ResearchBassel-Duby RCui MLiu NMalladi VSBezprozvannaya SJaichander PSanchez-Ortiz EWang ZOlson ENMin YLfalseIdentification of a multipotent Twist2-expressing cell population in the adult heart.Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from <i>Drosophila</i> to mammals. Through lineage tracing of Twist2 (Tw2)-expressing cells with tamoxifen-inducible Tw2-CreERT2 and tdTomato (tdTO) reporter mice, we discovered a unique cell population that progressively contributes to cardiomyocytes (CMs), endothelial cells, and fibroblasts in the adult heart. Clonal analysis confirmed the ability of Tw2-derived tdTO⁺ (Tw2-tdTO⁺) cells to form CMs in vitro. Within the adult heart, Tw2-tdTO⁺ CMs accounted for ∼13% of total CMs, the majority of which resulted from fusion of Tw2-tdTO⁺ cells with existing CMs. Tw2-tdTO⁺ cells also contribute to cardiac remodeling after injury. We co2018-01-01T00:00:00Z2018 Sep2026-05-03T22:28:31.659Z2019-08-04T08:13:26ZS-EPMC61303563012703310.1073/pnas.1800526115