Adventitial SCA-1+ progenitor cell gene sequencing reveals the mechanisms of cell migration in response to hyperlipidemia

Ioannis Kokkinopoulos, Mei Mei Wong, Claire M. F. Potter, Yao Xie, Baoqi Yu, Derek T. Warren, Witold N. Nowak, Alexandra Le Bras, Zhichao Ni, Chao Zhou, Xiongzhong Ruan, Eirini Karamariti, Yanhua Hu, Li Zhang, Qingbo Xu

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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.
Original languageEnglish
Pages (from-to)681–696
Number of pages16
JournalStem Cell Reports
Volume9
Issue number2
Early online date27 Jul 2017
DOIs
Publication statusPublished - 8 Aug 2017

Keywords

  • vascular progenitors
  • adventitial migration
  • hyperlipidemia
  • atherosclerosis
  • extracellular matrix

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