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Different populations of cardiovascular progenitor cells have been shown to possess varying differentiation potentials. They have also been used to facilitate heart repair. However, sensitive reporter cell lines that mark the human cardiovascular progenitors are in short supply. Methods: MESP1 marks the earliest population of cardiovascular progenitor cells during embryo development. Here, we generated a homozygous MESP1 knock-in reporter hESC line where mTomato gene joined to the MESP1 coding region via a 2A peptide, in which both MESP1 alleles were preserved. We performed transcriptome and functional analysis of human MESP1+ cardiovascular progenitor cells and tested their therapeutic potential using a rat model of myocardial infarction. Results: MESP1-mTomato knock-in reporter faithfully recapitulated the endogenous level of MESP1. Transcriptome analysis revealed that MESP1+ cells highly expressed early cardiovascular genes and heart development genes. The activation of MESP1 relied on the strength of canonical Wnt signaling, peak MESP1-mTomato fluorescence correlated with the window of canonical Wnt inhibition during in vitro differentiation. We further showed that MESP1 bound to the promoter of the WNT5A gene and the up-regulation of WNT5A expression suppressed canonical Wnt/β-CATENIN signaling. Moreover, induced MESP1 expression could substitute the canonical Wnt inhibition step and promote robust cardiomyocyte formation. We used a configurable, chemically defined, tri-lineage differentiation system to obtain cardiomyocytes, endothelial cells, and smooth muscle cells from MESP1+ cells at high efficiency. Finally, we showed that the engraftment of MESP1+ cells repaired rat myocardial infarction model. Conclusions: MESP1-mTomato reporter cells offered a useful platform to study cardiovascular differentiation from human pluripotent stem cells and explore their therapeutic potential in regenerative medicine.
Pubmed ID: 32550911
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Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
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