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.
Pubmed ID: 23939491 RIS Download
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An algorithm for the identification of microRNA targets. Details are provided (3' UTR alignments with predicted sites, links to various public databases etc) regarding: # microRNA target predictions in vertebrates (Krek et al, Nature Genetics 37:495-500 (2005)) # microRNA target predictions in seven Drosophila species (Grn et al, PLoS Comp. Biol. 1:e13 (2005)) # microRNA targets in three nematode species (Lall et al, Current Biology 16, 1-12 (2006)) # human microRNA targets that are not conserved but co-expressed (i.e. the microRNA and mRNA are expressed in the same tissue) (Chen and Rajewsky, Nat Genet 38, 1452-1456 (2006)) co-expressed targets
View all literature mentionsCatalogs of predicted microRNA targets in worm (based on ce6 genome assembly), fly (dm3), mouse (mm9) and human (hg18). We follow standard seed parameter settings and consider seeds of length 6-8 bases, beginning at position 2 of the microRNA. No mismatches or loops are allowed, but a single G:U wobble is allowed in 7- or 8-mers. In genes missing a 3' UTR annotation, 500 bp (fly), 800 bp (human and mouse) or 300 bp (worm) downstream of the annotated end of the coding sequence were used as the predicted UTR. For each organism, a catalog with zero flank and with a flank of 3 and 15 bases upstream and downstream.
View all literature mentionsData analysis service that predicts whether a given mRNA is targeted by a set of miRNAs. ComiR uses miRNA expression to improve and combine multiple miRNA targets for each of the four prediction algorithms: miRanda, PITA, TargetScan and mirSVR. The composite scores of the four algorithms are then combined using a support vector machine trained on Drosophila Ago1 IP data.
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