Journal article
Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development
Nature communications, Vol.16(1), 6947
07/29/2025
DOI: 10.1038/s41467-025-62208-9
PMCID: PMC12304165
PMID: 40721580
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.
Details
- Title: Subtitle
- Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development
- Creators
- Riley Leonard - University of IowaYi Zhao - Texas Heart Institute, Houston, TX, USASteven Eliason - University of IowaKathy Zimmerman - University of IowaAriana Batz - University of IowaCathy J Hatcher - Philadelphia College of Osteopathic MedicineRobert M Weiss - University of IowaMason Sweat - Harvard UniversityXiao Li - Texas Heart Institute, Houston, TX, USABrad A Amendt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.16(1), 6947
- DOI
- 10.1038/s41467-025-62208-9
- PMID
- 40721580
- PMCID
- PMC12304165
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- NATURE PORTFOLIO
- Grant note
- University of Iowa (UI)Iowa Institute of Human GeneticsUniversity of Iowa Cardiovascular Research CenterUniversity of Iowa Craniofacial Anomalies Research CenterUniversity of Iowa
The authors thank members of the Amendt laboratory for their expertise and helpful discussions and previous lab members for contributing to the study. We thank the Iowa Institute of Human Genetics (IIHG) Genomics Division for their help with sequencing, and the Flow Cytometry core for cell sorting to establish our stable cell lines. We thank the University of Iowa Cardiovascular Research Center and Cardiovascular Phenotyping Core for advice and support of this project. We also thank the University of Iowa Craniofacial Anomalies Research Center for their support. This work was supported by funding from the University of Iowa to BAA.
- Language
- English
- Date published
- 07/29/2025
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984905610602771
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