Adventitial SCA-1+ Progenitor Cell Gene Sequencing Reveals the Mechanisms of Cell Migration in Response to Hyperlipidemia

TY - JOUR

T1 - Adventitial SCA-1+ Progenitor Cell Gene Sequencing Reveals the Mechanisms of Cell Migration in Response to Hyperlipidemia

AU - Kokkinopoulos, Ioannis

AU - Wong, Mei Mei

AU - Potter, Claire M.F.

AU - Xie, Yao

AU - Yu, Baoqi

AU - Warren, Derek T.

AU - Nowak, Witold N.

AU - Le Bras, Alexandra

AU - Ni, Zhichao

AU - Zhou, Chao

AU - Ruan, Xiongzhong

AU - Karamariti, Eirini

AU - Hu, Yanhua

AU - Zhang, Li

AU - Xu, Qingbo

PY - 2017/8/8

Y1 - 2017/8/8

N2 - 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.

AB - 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.

KW - vascular progenitors

KW - adventitial migration

KW - hyperlipidemia

KW - atherosclerosis

KW - extracellular matrix

U2 - 10.1016/j.stemcr.2017.06.011

DO - 10.1016/j.stemcr.2017.06.011

M3 - Article

SN - 2213-6711

VL - 9

SP - 681-696,

JO - Stem cell reports

JF - Stem cell reports

IS - 2

ER -