Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8430-E8439. doi: 10.1073/pnas.1800526115. Epub 2018 Aug 20.
Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from 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 conclude that Tw2-tdTO cells participate in lifelong maintenance of cardiac function, at least in part through de novo formation of CMs and fusion with preexisting CMs, as well as in the genesis of other cellular components of the adult heart.
扭转型转录因子作为从 到哺乳动物等生物中中胚层细胞命运的祖调控因子发挥作用。通过使用他莫昔芬诱导型 Tw2-CreERT2 和 tdTomato（tdTO）报告小鼠对表达 Twist2（Tw2）的细胞进行谱系追踪，我们发现了一种独特的细胞群，该细胞群逐渐成为成年心脏中的心肌细胞（CMs）、内皮细胞和成纤维细胞的来源。克隆分析证实了 Tw2 衍生的 tdTO（Tw2-tdTO）细胞在体外形成 CMs 的能力。在成年心脏中，Tw2-tdTO CMs 约占总 CMs 的 13%，其中大部分是由 Tw2-tdTO 细胞与现有 CMs 的融合产生的。Tw2-tdTO 细胞在损伤后也有助于心脏重塑。我们得出结论，Tw2-tdTO 细胞参与心脏功能的终生维持，至少部分是通过新形成的 CMs 与现有 CMs 的融合以及成年心脏其他细胞成分的产生来实现的。
