Language
English
Publication Date
7-29-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-62208-9
PMID
40721580
PMCID
PMC12304165
PubMedCentral® Posted Date
7-29-2025
PubMedCentral® Full Text Version
Post-print
Abstract
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.
Keywords
Animals, Myocytes, Cardiac, MicroRNAs, Mice, Heart, Cell Differentiation, Transcription Factors, Gene Expression Regulation, Developmental, GATA4 Transcription Factor, T-Box Domain Proteins, Homeodomain Proteins, MEF2 Transcription Factors, Homeobox Protein PITX2, Single-Cell Analysis, Multiomics, Heart development, Cell lineage
Published Open-Access
yes
Recommended Citation
Leonard, Riley; Zhao, Yi; Eliason, Steven; et al., "Single-Nuclei Multiomics Analysis Identifies Abnormal Cardiomyocytes in a Murine Model of Cardiac Development" (2025). Faculty, Staff and Students Publications. 8590.
https://digitalcommons.library.tmc.edu/baylor_docs/8590