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

Ioannis Kokkinopoulos, Mei Mei Wong, Claire MF 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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