Direct reprogramming of fibroblasts identifies signatures of vascular dysfunction in physiological aging and Hutchinson-Gilford Progeria Syndrome

Our goal was to identify gene expression and functional differences between directly reprogrammed vascular cells derived from young and old individuals, as wells as from healthy and Hutchinson-Gilford Progeria Syndrome (HGPS) donors. We provided a full characterization of reprogrammed endothelial and smooth muscle cells by comparing their gene expression with both the original fibroblasts and primary vascular cells, showing that reprogrammed cells express key vascular cell-identity genes and contribute to the formation of in vitro 3D vascular structures. We identified and validated biomarkers of vascular dysfunction in the context of physiological and accelerated aging typical of HGPS patients, and we demonstrated their direct contribution in the modulation of vascular permeability. Overall design: We performed RNAseq on directly reprogrammed vascular cells (induced vascular endothelial cells (iVECs) and induced smooth muscle (iSM) cells). We compared directly reprogrammed cells with the original fibroblasts as well as with primary vascular cells. Furthemore, we compared directly reprogrammed cells obtained from healthy young vs. old donors (N=3 per group) as wells as from Hutchinson Gilford Progeria Syndrome (HGPS) (N=8) vs. healthy (N=3) donors. This series includes the re-analysis of GSM3175518, GSM3175519 and GSM3175520.