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

• Published in: Cell death discovery Vol. 7; no. 1; pp. 180 - 14
• Main Authors: Li, Fengchan, Yan, Kunmin, Wu, Lili, Zheng, Zhong, Du, Yun, Liu, Ziting, Zhao, Luyao, Li, Wei, Sheng, Yulan, Ren, Lijie, Tang, Chaojun, Zhu, Li
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.07.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/61; 631/80; Aorta; Apoptosis; Arteriosclerosis; Atherosclerosis; Biochemistry; Biomedical and Life Sciences; Blood flow; Carotid arteries; Carotid artery; CD4 antigen; Cell Biology; Cell Cycle Analysis; Endothelial cells; Gene expression; Leukocytes (granulocytic); Life Sciences; Lymphocytes T; Macrophages; Osteoblastogenesis; Stem Cells; Veins & arteries
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-021-00567-0

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 Mφ, Birc5 hi Mφ, DCs, CD4 + T cells, CXCR6 + T cells, NK cells, and granulocytes were identified under d-flow. Of note, the novel Birc5 hi Mφ 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.