title: In Vitro Generation of Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature from Murine Induced Pluripotent Stem Cells.
abstract: The vascular wall (VW) serves as a niche for mesenchymal stem cells (MSCs). In general, tissue-specific stem cells differentiate mainly to the tissue type from which they derive, indicating that there is a certain code or priming within the cells as determined by the tissue of origin. Here we report the in vitro generation of VW-typical MSCs from induced pluripotent stem cells (iPSCs), based on a VW-MSC-specific gene code. Using a lentiviral vector expressing the so-called Yamanaka factors, we reprogrammed tail dermal fibroblasts from transgenic mice containing the GFP gene integrated into the Nestin-locus (NEST-iPSCs) to facilitate lineage tracing after subsequent MSC differentiation. A lentiviral vector expressing a small set of recently identified human VW-MSC-specific HOX genes then induced MSC differentiation. This direct programming approach successfully mediated the generation of VW-typical MSCs with classical MSC characteristics, both in vitro and in vivo.
authors.affiliation: Institute of Cell Biology (Cancer Research), University Hospital Essen, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Steens
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Zuk
authors.affiliation: Institute of Cell Biology (Cancer Research), University Hospital Essen, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benchellal
authors.affiliation: Institute of Cell Biology (Cancer Research), University Hospital Essen, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Bornemann
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Teichweyde
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hess
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Görgens
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Klump
authors.affiliation: Institute of Cell Biology (Cancer Research), University Hospital Essen, Medical Faculty, University of Duisburg-Essen, 45122 Essen, Germany. Electronic address: diana.klein@uk-essen.de.
authors.forename: Diana
authors.initials: D
authors.lastname: Klein
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005801:Genes, Homeobox; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
keywords: HOX gene; direct programming; induced pluripotent stem cells; nestin; vascular wall-derived mesenchymal stem cells