In?Vitro Generation of Vascular Wall-Resident Multipotent Stem Cells of?Mesenchymal Nature from Murine Induced Pluripotent Stem Cells

摘要

Highlights ? In?vitro generation of (VW)-typical MSCs from iPSCs based on a specific HOX code ? Reprogrammed fibroblasts (NEST-iPSCs) facilitated lineage tracing ? A lentiviral vector expressing HOXB7 , HOXC6 , and HOXC8 induced MSC differentiation ? Generated VW-MSCs showed classical MSC characteristics in?vitro and in?vivo Summary 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.