Leonard Riley, Zhao Yi, Eliason Steven, Zimmerman Kathy, Batz Ariana, Hatcher Cathy J, Weiss Robert M, Sweat Mason, Li Xiao, Amendt Brad A
The University of Iowa, Department of Anatomy and Cell Biology, Iowa City, IA, USA.
Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA, USA.
Nat Commun. 2025 Jul 29;16(1):6947. doi: 10.1038/s41467-025-62208-9.
Transcription factors such as Tbx5, Gata4, Mef2c and Pitx2 are required during cardiac development, and in adult cardiac homeostasis. We demonstrate that the gene dosage and modulation of these factors are mediated in vivo by the miR-200 family. Inhibition of a single miR-200 family member within the cluster results in defects of the left ventricle and cardiomyocyte maturation during development. Inhibition of the entire miR-200 family results in a ventricular septal defect and embryonic lethality by embryonic day (E)16.5. Inhibition of each miR-200 family has distinct heart phenotypes in cell specific differentiation and maturation. snRNA-sequencing reveals an immature cardiomyocyte cell state, suggesting reduced differentiation of these cells. The miR-200 family members are critical regulators of early cardiac development through maintaining cardiomyocyte differentiation and maturation. In this report, we identify several transcription factors regulated by miR-200 during heart development, a role for miR-200 in specific heart defects, and an abnormal cardiomyocyte population.
转录因子如Tbx5、Gata4、Mef2c和Pitx2在心脏发育过程以及成体心脏稳态维持中发挥作用。我们证明，这些因子的基因剂量和调控在体内由miR-200家族介导。在该基因簇内抑制单个miR-200家族成员会导致发育过程中左心室和心肌细胞成熟缺陷。抑制整个miR-200家族会导致室间隔缺损，并在胚胎期第16.5天出现胚胎致死。抑制每个miR-200家族成员在细胞特异性分化和成熟过程中具有不同的心脏表型。snRNA测序揭示了未成熟的心肌细胞状态，表明这些细胞的分化减少。miR-200家族成员通过维持心肌细胞的分化和成熟，是早期心脏发育的关键调节因子。在本报告中，我们确定了心脏发育过程中受miR-200调控的几种转录因子、miR-200在特定心脏缺陷中的作用以及异常的心肌细胞群体。
