Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways
| Autor: | Cheng Cui, Tung-Ying Lu, Arshi Arora, Lei Yang, Yi Sheng, Claudia Coronnello, Yang Li, Bo Lin, Lu Han, Panayiotis V. Benos |
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| Rok vydání: | 2013 |
| Předmět: |
Mesoderm
Frizzled Cellular differentiation Genetic Vectors Induced Pluripotent Stem Cells Gene Expression Biology Fibroblast growth factor Models Biological Article Mice Gene Order medicine Animals Humans Myocytes Cardiac Progenitor cell Induced pluripotent stem cell Molecular Biology Base Pairing Embryonic Stem Cells Adaptor Proteins Signal Transducing Base Sequence Gene Expression Profiling Wnt signaling pathway Membrane Proteins Reproducibility of Results Cell Differentiation Embryonic stem cell Molecular biology Frizzled Receptors Cell biology Fibroblast Growth Factors Wnt Proteins MicroRNAs medicine.anatomical_structure RNA Interference Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Journal of molecular and cellular cardiology. 63 |
| ISSN: | 1095-8584 |
| Popis: | Early heart development takes place through a complex series of steps, including the induction of cardiac mesoderm, formation of the cardiovascular progenitor cells and the commitment of cardiovascular lineage cells, such as cardiomyocytes (CMs), smooth muscle cells (SMCs) and endothelial cells (ECs). Recently, microRNAs, a family of endogenous, small non-coding RNAs, have been implicated as critical regulators at the posttranscriptional level in cardiogenesis as well as cardiovascular disease. Previous studies demonstrated that microRNA-1 (miR-1) could promote cardiac differentiation from mouse and human embryonic stem (ES) cells. However, the underlying mechanism largely remained unclear. We performed microRNA deep sequencing among human ES cells, ES cell derived-multipotent cardiovascular progenitors (MCPs), and MCP-specified CMs, ECs, and SMCs. A specific enrichment of miR-1 was found in CMs, not in SMCs or ECs, implying a key role of miR-1 in determining cardiovascular commitment from MCPs. When overexpressed in human pluripotent stem cells, miR-1 enhanced the expression of key cardiac transcriptional factors and sarcomeric genes. Importantly, we found miR-1 promoted CM differentiation and suppressed EC commitment from MCPs by modulating the activities of WNT and FGF signaling pathways. FZD7 and FRS2 were confirmed as miR-1 targets using luciferase reporter assay and western blot. Overall, this study reveals a switch role of miR-1 at early human cardiovascular commitment stage via suppressing both WNT and FGF signaling pathways. |
| Databáze: | OpenAIRE |
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