1. miR-322/-503 cluster is expressed in the earliest cardiac progenitor cells and drives cardiomyocyte specification
- Author
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Wei Yu, Peijun Liu, Rui Liang, Ashley Benham, Xueping Xu, Robert J. Schwartz, Benjamin Soibam, Mark Mercola, Xiaopeng Shen, Yu Liu, Mani Chopra, Alon Azares, Wenjing Bao, Xiaoping Peng, Preethi H. Gunaratne, and Austin J. Cooney
- Subjects
0301 basic medicine ,Mesoderm ,RNA, Untranslated ,Cellular differentiation ,Primary Cell Culture ,Mice, Transgenic ,03 medical and health sciences ,Mice ,Bacterial Proteins ,Genes, Reporter ,microRNA ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Morphogenesis ,Animals ,Cell Lineage ,Myocytes, Cardiac ,Gene ,CELF1 Protein ,Multidisciplinary ,biology ,Integrases ,Regeneration (biology) ,Gene Expression Profiling ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Biological Sciences ,Embryo, Mammalian ,Molecular biology ,Cell biology ,Gene expression profiling ,Luminescent Proteins ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Histone ,biology.protein ,Signal transduction ,Signal Transduction - Abstract
Understanding the mechanisms of early cardiac fate determination may lead to better approaches in promoting heart regeneration. We used a mesoderm posterior 1 (Mesp1)-Cre/Rosa26-EYFP reporter system to identify microRNAs (miRNAs) enriched in early cardiac progenitor cells. Most of these miRNA genes bear MESP1-binding sites and active histone signatures. In a calcium transient-based screening assay, we identified miRNAs that may promote the cardiomyocyte program. An X-chromosome miRNA cluster, miR-322/-503, is the most enriched in the Mesp1 lineage and is the most potent in the screening assay. It is specifically expressed in the looping heart. Ectopic miR-322/-503 mimicking the endogenous temporal patterns specifically drives a cardiomyocyte program while inhibiting neural lineages, likely by targeting the RNA-binding protein CUG-binding protein Elav-like family member 1 (Celf1). Thus, early miRNAs in lineage-committed cells may play powerful roles in cell-fate determination by cross-suppressing other lineages. miRNAs identified in this study, especially miR-322/-503, are potent regulators of early cardiac fate.
- Published
- 2016