Faculty Collaboration Database

Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways. J Mol Cell Cardiol 2013 Oct;63:146-54

Date

08/14/2013

Pubmed ID

23939491

Pubmed Central ID

PMC4268488

DOI

10.1016/j.yjmcc.2013.07.019

Scopus ID

2-s2.0-84883118146 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

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 identified as critical regulators in cardiogenesis and 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 remained largely 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 induced 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 fate-switching role of miR-1 at early human cardiovascular commitment stage via suppressing both WNT and FGF signaling pathways.

Author List

Lu TY, Lin B, Li Y, Arora A, Han L, Cui C, Coronnello C, Sheng Y, Benos PV, Yang L

Author

Lu Han PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Animals
Base Pairing
Base Sequence
Cell Differentiation
Embryonic Stem Cells
Fibroblast Growth Factors
Frizzled Receptors
Gene Expression
Gene Expression Profiling
Gene Order
Genetic Vectors
Humans
Induced Pluripotent Stem Cells
Membrane Proteins
Mice
MicroRNAs
Models, Biological
Myocytes, Cardiac
RNA Interference
Reproducibility of Results
Signal Transduction
Wnt Proteins