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Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development

Author

Listed:
  • Riley Leonard

    (Department of Anatomy and Cell Biology
    The University of Iowa)

  • Yi Zhao

    (Texas Heart Institute)

  • Steven Eliason

    (Department of Anatomy and Cell Biology
    The University of Iowa)

  • Kathy Zimmerman

    (Department of Internal Medicine)

  • Ariana Batz

    (Department of Internal Medicine)

  • Cathy J. Hatcher

    (Philadelphia College of Osteopathic Medicine)

  • Robert M. Weiss

    (Department of Internal Medicine
    Department of Veteran Affairs)

  • Mason Sweat

    (Harvard University)

  • Xiao Li

    (Texas Heart Institute)

  • Brad A. Amendt

    (Department of Anatomy and Cell Biology
    The University of Iowa)

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.

Suggested Citation

  • Riley Leonard & Yi Zhao & Steven Eliason & Kathy Zimmerman & Ariana Batz & Cathy J. Hatcher & Robert M. Weiss & Mason Sweat & Xiao Li & Brad A. Amendt, 2025. "Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62208-9
    DOI: 10.1038/s41467-025-62208-9
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