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Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors

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Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors. / Deng, Jiacheng; Ni, Zhichao; Gu, Wenduo; Chen, Qishan; Nowak, Witold Norbert; Chen, Ting; Issa Bhaloo, Shirin; Zhang, Zhongyi; Hu, Yanhua; Zhou, Bin; Zhang, Li; Xu, Qingbo.

In: Cellular and Molecular Life Sciences, 01.01.2020.

Research output: Contribution to journalArticle

Harvard

Deng, J, Ni, Z, Gu, W, Chen, Q, Nowak, WN, Chen, T, Issa Bhaloo, S, Zhang, Z, Hu, Y, Zhou, B, Zhang, L & Xu, Q 2020, 'Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors', Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-020-03480-4

APA

Deng, J., Ni, Z., Gu, W., Chen, Q., Nowak, W. N., Chen, T., ... Xu, Q. (Accepted/In press). Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors. Cellular and Molecular Life Sciences. https://doi.org/10.1007/s00018-020-03480-4

Vancouver

Deng J, Ni Z, Gu W, Chen Q, Nowak WN, Chen T et al. Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors. Cellular and Molecular Life Sciences. 2020 Jan 1. https://doi.org/10.1007/s00018-020-03480-4

Author

Deng, Jiacheng ; Ni, Zhichao ; Gu, Wenduo ; Chen, Qishan ; Nowak, Witold Norbert ; Chen, Ting ; Issa Bhaloo, Shirin ; Zhang, Zhongyi ; Hu, Yanhua ; Zhou, Bin ; Zhang, Li ; Xu, Qingbo. / Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors. In: Cellular and Molecular Life Sciences. 2020.

Bibtex Download

@article{ed1931f01d4a4163934a1ca204363043,
title = "Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors",
abstract = "Stem/progenitor cells (SPCs) have been implicated to participate in vascular repair. However, the exact role of SPCs in endothelial repair of large vessels still remains controversial. This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing (scRNA-seq) and genetic lineage tracing mouse models, we uncovered the cellular heterogeneity of SPCs, i.e., c-Kit+ cells in the mouse aorta, and found that endogenous c-Kit+ cells acquire endothelial cell fate in the aorta under both physiological and pathological conditions. While c-Kit+ cells contribute to aortic endothelial turnover in the atheroprone regions during homeostasis, recipient c-Kit+ cells of nonbone marrow source replace both luminal and microvessel endothelial cells in transplant arteriosclerosis. Single-cell pseudotime analysis of scRNA-seq data and in vitro cell experiments suggest that vascular SPCs display endothelial differentiation potential and undergo metabolic reprogramming during cell differentiation, in which AKT/mTOR-dependent glycolysis is critical for endothelial gene expression. These findings demonstrate a critical role for c-Kit lineage cells in aortic endothelial turnover and replacement, and may provide insights into therapeutic strategies for vascular diseases.",
keywords = "Endothelial repair, Lineage tracing, Metabolism, Single-cell RNA-sequencing, Stem cells",
author = "Jiacheng Deng and Zhichao Ni and Wenduo Gu and Qishan Chen and Nowak, {Witold Norbert} and Ting Chen and {Issa Bhaloo}, Shirin and Zhongyi Zhang and Yanhua Hu and Bin Zhou and Li Zhang and Qingbo Xu",
year = "2020",
month = "1",
day = "1",
doi = "10.1007/s00018-020-03480-4",
language = "English",
journal = "Cellular and molecular life sciences : CMLS",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors

AU - Deng, Jiacheng

AU - Ni, Zhichao

AU - Gu, Wenduo

AU - Chen, Qishan

AU - Nowak, Witold Norbert

AU - Chen, Ting

AU - Issa Bhaloo, Shirin

AU - Zhang, Zhongyi

AU - Hu, Yanhua

AU - Zhou, Bin

AU - Zhang, Li

AU - Xu, Qingbo

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Stem/progenitor cells (SPCs) have been implicated to participate in vascular repair. However, the exact role of SPCs in endothelial repair of large vessels still remains controversial. This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing (scRNA-seq) and genetic lineage tracing mouse models, we uncovered the cellular heterogeneity of SPCs, i.e., c-Kit+ cells in the mouse aorta, and found that endogenous c-Kit+ cells acquire endothelial cell fate in the aorta under both physiological and pathological conditions. While c-Kit+ cells contribute to aortic endothelial turnover in the atheroprone regions during homeostasis, recipient c-Kit+ cells of nonbone marrow source replace both luminal and microvessel endothelial cells in transplant arteriosclerosis. Single-cell pseudotime analysis of scRNA-seq data and in vitro cell experiments suggest that vascular SPCs display endothelial differentiation potential and undergo metabolic reprogramming during cell differentiation, in which AKT/mTOR-dependent glycolysis is critical for endothelial gene expression. These findings demonstrate a critical role for c-Kit lineage cells in aortic endothelial turnover and replacement, and may provide insights into therapeutic strategies for vascular diseases.

AB - Stem/progenitor cells (SPCs) have been implicated to participate in vascular repair. However, the exact role of SPCs in endothelial repair of large vessels still remains controversial. This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing (scRNA-seq) and genetic lineage tracing mouse models, we uncovered the cellular heterogeneity of SPCs, i.e., c-Kit+ cells in the mouse aorta, and found that endogenous c-Kit+ cells acquire endothelial cell fate in the aorta under both physiological and pathological conditions. While c-Kit+ cells contribute to aortic endothelial turnover in the atheroprone regions during homeostasis, recipient c-Kit+ cells of nonbone marrow source replace both luminal and microvessel endothelial cells in transplant arteriosclerosis. Single-cell pseudotime analysis of scRNA-seq data and in vitro cell experiments suggest that vascular SPCs display endothelial differentiation potential and undergo metabolic reprogramming during cell differentiation, in which AKT/mTOR-dependent glycolysis is critical for endothelial gene expression. These findings demonstrate a critical role for c-Kit lineage cells in aortic endothelial turnover and replacement, and may provide insights into therapeutic strategies for vascular diseases.

KW - Endothelial repair

KW - Lineage tracing

KW - Metabolism

KW - Single-cell RNA-sequencing

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=85081929889&partnerID=8YFLogxK

U2 - 10.1007/s00018-020-03480-4

DO - 10.1007/s00018-020-03480-4

M3 - Article

C2 - 32166394

AN - SCOPUS:85081929889

JO - Cellular and molecular life sciences : CMLS

JF - Cellular and molecular life sciences : CMLS

SN - 1420-682X

ER -

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