Kokkinopoulos, I; Wong, MM; Potter, CMF; Xie, Y; Yu, B; Warren, DT; Nowak, WN; ... Xu, Q; + view all Kokkinopoulos, I; Wong, MM; Potter, CMF; Xie, Y; Yu, B; Warren, DT; Nowak, WN; Le Bras, A; Ni, Z; Zhou, C; Ruan, X; Karamariti, E; Hu, Y; Zhang, L; Xu, Q; - view fewer (2017) Adventitial SCA-1(+) Progenitor Cell Gene Sequencing Reveals the Mechanisms of Cell Migration in Response to Hyperlipidemia. Stem Cell Reports , 9 (2) pp. 681-696. 10.1016/j.stemcr.2017.06.011.

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Abstract

Adventitial progenitor cells, including SCA-1+ and mesenchymal stem cells, are believed to be important in vascular remodeling. It has been shown that SCA-1+ progenitor cells are involved in neointimal hyperplasia of vein grafts, but little is known concerning their involvement in hyperlipidemia-induced atherosclerosis. We employed single-cell sequencing technology on primary adventitial mouse SCA-1+ cells from wild-type and atherosclerotic-prone (ApoE-deficient) mice and found that a group of genes controlling cell migration and matrix protein degradation was highly altered. Adventitial progenitors from ApoE-deficient mice displayed an augmented migratory potential both in vitro and in vivo. This increased migratory ability was mimicked by lipid loading to SCA-1+ cells. Furthermore, we show that lipid loading increased miRNA-29b expression and induced sirtuin-1 and matrix metalloproteinase-9 levels to promote cell migration. These results provide direct evidence that blood cholesterol levels influence vascular progenitor cell function, which could be a potential target cell for treatment of vascular disease.

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