4.6 Article

Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow

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CELL DEATH DISCOVERY
卷 7, 期 1, 页码 -

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SPRINGERNATURE
DOI: 10.1038/s41420-021-00567-0

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资金

  1. Natural Science Foundation of China [81620108001, 81870325, 91739302, 82070450, 81670134]
  2. Natural Science Foundation of Jiangsu Province [BK20201410]
  3. Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX21_2967]
  4. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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The study showed that disturbed blood flow can alter arterial wall cells, increasing the risk of atherosclerosis. Single-cell RNA sequencing revealed multiple cell subpopulations related to disturbed blood flow, including mechanosensitive endothelial cells and smooth muscle cells potentially impacting arterial stiffness.
Disturbed blood flow (d-flow) has been known to induce changes of the cells in the arterial wall, increasing the risk of atherosclerosis. However, the heterogeneity of the vascular cell populations under d-flow remains less understood. To generate d-flow in vivo, partial carotid artery ligation (PCL) was performed. Seven days after ligation, single-cell RNA sequencing of nine left carotid arteries (LCA) from the PCL group (10,262 cells) or control group (14,580 cells) was applied and a single-cell atlas of gene expression was constructed. The integrated analysis identified 15 distinct carotid cell clusters, including 10 d-flow-relevant subpopulations. Among endothelial cells, at least four subpopulations were identified, including Klk8(hi) ECs, Lrp1(hi) ECs, Dkk2(hi) ECs, and Cd36(hi) ECs. Analysis of GSVA and single-cell trajectories indicated that the previously undescribed Dkk2(hi) ECs subpopulation was mechanosensitive and potentially transformed from Klk8(hi) ECs under d-flow. D-flow-induced Spp1(hi) VSMCs subpopulation that appeared to be endowed with osteoblast differentiation, suggesting a role in arterial stiffness. Among the infiltrating cell subpopulations, Trem2(hi) M phi, Birc5(hi) M phi, DCs, CD4(+) T cells, CXCR6(+) T cells, NK cells, and granulocytes were identified under d-flow. Of note, the novel Birc5(hi) M phi was identified as a potential contributor to the accumulation of macrophages in atherosclerosis. Finally, Dkk2(hi) ECs, and Cd36(hi) ECs were also found in the proatherosclerotic area of the aorta where the d-flow occurs. In conclusion, we presented a comprehensive single-cell atlas of all cells in the carotid artery under d-flow, identified previously unrecognized cell subpopulations and their gene expression signatures, and suggested their specialized functions.

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