title: Selection of a common multipotent cardiovascular stem cell using the 3.4-kb MesP1 promoter fragment.
abstract: Common cardiovascular progenitor cells are characterized and induced by expression of the transcription factor MesP1. To characterize this population we used a 3.4-kb promoter fragment previously described by our group. This served to isolate MesP1-positive cells from differentiating ES stem cells via magnetic cell sorting based on a truncated CD4 surface marker. As this proximal promoter fragment omits a distal non-cardiovasculogenic enhancer region, we were able to achieve a synchronized fraction of highly enriched cardiovascular progenitors. These led to about 90% of cells representing the three cardiovascular lineages: cardiomyocytes, endothelial cells and smooth muscle cells as evident from protein and mRNA analyses. In addition, electrophysiological and pharmacological parameters of the cardiomyocytic fraction show that almost all correspond to the multipotent early/intermediate cardiomyocyte subtype at day 18 of differentiation. Further differentiation of these cells was not impaired as evident from strong and synchronous beating at later stages. Our work contributes to the understanding of the earliest cardiovasculogenic events and may become an important prerequisite for cell therapy, tissue engineering and pharmacological testing in the culture dish using pluripotent stem cell-derived as well as directly reprogrammed cardiovascular cell types. Likewise, these cells provide an ideal source for large-scale transcriptome and proteome analyses.
authors.affiliation: Referenz- und Translationszentrum für Kardiale Stammzelltherapie der Universität Rostock, 18057 Rostock, Germany. robert.david@med.uni-rostock.de
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Florian
authors.initials: F
authors.lastname: Schwarz
authors.forename: Christian
authors.initials: C
authors.lastname: Rimmbach
authors.forename: Petra
authors.initials: P
authors.lastname: Nathan
authors.forename: Julia
authors.initials: J
authors.lastname: Jung
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenner
authors.forename: Veronica
authors.initials: V
authors.lastname: Jarsch
authors.forename: Juliane
authors.initials: J
authors.lastname: Stieber
authors.forename: Wolfgang-Michael
authors.initials: WM
authors.lastname: Franz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002319:Cardiovascular System / Q000166:cytology*; D002454:Cell Differentiation; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D011401:Promoter Regions, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C101538:Mesp1 protein, mouse