title: miR-322/-503 cluster is expressed in the earliest cardiac progenitor cells and drives cardiomyocyte specification.
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.
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Xiaopeng
authors: X
authors: Shen
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004; Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030;
authors: Benjamin
authors: B
authors: Soibam
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004; Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030;
authors: Ashley
authors: A
authors: Benham
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;
authors: Xueping
authors: X
authors: Xu
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Mani
authors: M
authors: Chopra
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Xiaoping
authors: X
authors: Peng
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Wei
authors: W
authors: Yu
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Wenjing
authors: W
authors: Bao
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Rui
authors: R
authors: Liang
authors: Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030;
authors: Alon
authors: A
authors: Azares
authors: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, Peoples' Republic of China;
authors: Peijun
authors: P
authors: Liu
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004;
authors: Preethi H
authors: PH
authors: Gunaratne
authors: Department of Bioengineering, Jacobs School of Engineering, University of California at San Diego, La Jolla, CA 92093.
authors: Mark
authors: M
authors: Mercola
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;
authors: Austin J
authors: AJ
authors: Cooney
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004; Stem Cell Engineering, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77030;
authors: Robert J
authors: RJ
authors: Schwartz
authors: Department of Biology and Biochemistry, University of Houston, Houston, TX 77004; yliu54@uh.edu.
authors: Yu
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D000067879:CELF1 Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D000067879:CELF1 Protein; D019426:Integrases; D008164:Luminescent Proteins; D035683:MicroRNAs; D022661:RNA, Untranslated; C502743:CELF1 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C582672:MIRN322 microRNA, mouse; C101538:Mesp1 protein, mouse; C556275:Mirn503 microRNA, mouse; C054562:yellow fluorescent protein, Bacteria; C045073:Cre recombinase
keywords: cardiomyocyte; miR-322; miR-424; miR-503; microRNA