Adipose tissue-derived stromal cells acquire endothelial-like features upon reprogramming with SOX18

• Endothelial-specific SOX18 was expressed in adipose tissue-derived stromal cells.
• Expression of SOX18 induces KDR, CD34 and vascular patterning genes.
• SOX18-transduced ASCs respond to VEGF and shear stress.
• SOX18-transduced ASCs form tubular structures that show lumen formation.

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.