Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow
Abstract 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 liga...
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Series: | Cell Death Discovery |
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doaj-db3d0d915a754b4f8a92868d76240f0f2021-07-25T11:11:43ZengNature Publishing GroupCell Death Discovery2058-77162021-07-017111410.1038/s41420-021-00567-0Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flowFengchan Li0Kunmin Yan1Lili Wu2Zhong Zheng3Yun Du4Ziting Liu5Luyao Zhao6Wei Li7Yulan Sheng8Lijie Ren9Chaojun Tang10Li Zhu11Cyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterCyrus Tang Hematology CenterAbstract 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 Klk8hi ECs, Lrp1hi ECs, Dkk2hi ECs, and Cd36hi ECs. Analysis of GSVA and single-cell trajectories indicated that the previously undescribed Dkk2hi ECs subpopulation was mechanosensitive and potentially transformed from Klk8hi ECs under d-flow. D-flow-induced Spp1hi VSMCs subpopulation that appeared to be endowed with osteoblast differentiation, suggesting a role in arterial stiffness. Among the infiltrating cell subpopulations, Trem2hi Mφ, Birc5hi Mφ, DCs, CD4+ T cells, CXCR6+ T cells, NK cells, and granulocytes were identified under d-flow. Of note, the novel Birc5hi Mφ was identified as a potential contributor to the accumulation of macrophages in atherosclerosis. Finally, Dkk2hi ECs, and Cd36hi 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.https://doi.org/10.1038/s41420-021-00567-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fengchan Li Kunmin Yan Lili Wu Zhong Zheng Yun Du Ziting Liu Luyao Zhao Wei Li Yulan Sheng Lijie Ren Chaojun Tang Li Zhu |
spellingShingle |
Fengchan Li Kunmin Yan Lili Wu Zhong Zheng Yun Du Ziting Liu Luyao Zhao Wei Li Yulan Sheng Lijie Ren Chaojun Tang Li Zhu Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow Cell Death Discovery |
author_facet |
Fengchan Li Kunmin Yan Lili Wu Zhong Zheng Yun Du Ziting Liu Luyao Zhao Wei Li Yulan Sheng Lijie Ren Chaojun Tang Li Zhu |
author_sort |
Fengchan Li |
title |
Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow |
title_short |
Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow |
title_full |
Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow |
title_fullStr |
Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow |
title_full_unstemmed |
Single-cell RNA-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow |
title_sort |
single-cell rna-seq reveals cellular heterogeneity of mouse carotid artery under disturbed flow |
publisher |
Nature Publishing Group |
series |
Cell Death Discovery |
issn |
2058-7716 |
publishDate |
2021-07-01 |
description |
Abstract 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 Klk8hi ECs, Lrp1hi ECs, Dkk2hi ECs, and Cd36hi ECs. Analysis of GSVA and single-cell trajectories indicated that the previously undescribed Dkk2hi ECs subpopulation was mechanosensitive and potentially transformed from Klk8hi ECs under d-flow. D-flow-induced Spp1hi VSMCs subpopulation that appeared to be endowed with osteoblast differentiation, suggesting a role in arterial stiffness. Among the infiltrating cell subpopulations, Trem2hi Mφ, Birc5hi Mφ, DCs, CD4+ T cells, CXCR6+ T cells, NK cells, and granulocytes were identified under d-flow. Of note, the novel Birc5hi Mφ was identified as a potential contributor to the accumulation of macrophages in atherosclerosis. Finally, Dkk2hi ECs, and Cd36hi 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. |
url |
https://doi.org/10.1038/s41420-021-00567-0 |
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