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miR-322/-503 cluster is expressed in the earliest cardiac progenitor cells and drives cardiomyocyte specification
- Publication Year :
- 2016
- Publisher :
- National Academy of Sciences, 2016.
-
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.
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....34e89ae73525893e836b1797353dc1eb