title: Adipose tissue-derived stromal cells acquire endothelial-like features upon reprogramming with SOX18.
abstract: Adipose tissue-derived stromal cells (ASC) form a rich source of autologous cells for use in regenerative medicine. In vitro induction of an endothelial phenotype may improve performance of ASCs in cardiovascular repair. Here, we report on an in vitro strategy using direct reprogramming of ASCs by means of ectopic expression of the endothelial-specific transcription factor SRY (sex determining region Y)-box18 (SOX18). SOX18 induces ASCs to express a set of genes involved in vascular patterning: MMP7, KDR, EFNB2, SEMA3G and CXCR4. Accordingly, SOX18 transduced ASCs reorganize under conditions of shear stress, display VEGF-induced chemotaxis and form tubular structures in 3D matrices in an MMP7-dependent manner. These in vitro findings provide insight into molecular and cellular processes downstream of SOX18 and show that reprogramming using SOX18 is sufficient to induce several endothelial-like features in ASCs.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: r.fontijn@vumc.nl.
authors.forename: R D
authors.initials: RD
authors.lastname: Fontijn
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: julie.favre22@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Favre
authors.affiliation: Department of Pathology and Cardiac Surgery, VU University Medical Center, de Boelelaan 117, 1081 HV Amsterdam, The Netherlands. Electronic address: b.naaijkens@vumc.nl.
authors.forename: B A
authors.initials: BA
authors.lastname: Naaijkens
authors.affiliation: Department of Pathology and Cardiac Surgery, VU University Medical Center, de Boelelaan 117, 1081 HV Amsterdam, The Netherlands. Electronic address: e.meinster@vumc.nl.
authors.forename: E
authors.initials: E
authors.lastname: Meinster
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: nj.paauw@vumc.nl.
authors.forename: N J
authors.initials: NJ
authors.lastname: Paauw
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: S L
authors.initials: SL
authors.lastname: Ragghoe
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: t.nauta@vumc.nl.
authors.forename: T D
authors.initials: TD
authors.lastname: Nauta
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: ma.vandenbroek@vumc.nl.
authors.forename: M A
authors.initials: MA
authors.lastname: van den Broek
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: e.weijers@vumc.nl.
authors.forename: E M
authors.initials: EM
authors.lastname: Weijers
authors.affiliation: Department of Pathology and Cardiac Surgery, VU University Medical Center, de Boelelaan 117, 1081 HV Amsterdam, The Netherlands. Electronic address: jwm.niessen@vumc.nl.
authors.forename: H W
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: p.koolwijk@vumc.nl.
authors.forename: P
authors.initials: P
authors.lastname: Koolwijk
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Electronic address: aj.horrevoets@vumc.nl.
authors.forename: A J
authors.initials: AJ
authors.lastname: Horrevoets
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D033081:Shear Strength; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7