Single-cell analysis reveals the implication of vascular endothelial cell-intrinsic ANGPT2 in human intracranial aneurysm

doi:10.1093/cvr/cvae186

	Single-cell analysis reveals the implication of vascular endothelial cell-intrinsic ANGPT2 in human intracranial aneurysm
	Yu, Guo 1,3,4,5,6; Li, Jia 2; Zhang, Hongfei 1,3,4,5,6; Zi, Huaxing 2,7; Liu, Mingjian 1,3,4,5,6; An, Qingzhu 1,3,4,5,6; Qiu, Tianming 1,3,4,5,6; Li, Peiliang 1,3,4,5,6; Song, Jianping 1,3,4,5,6; Liu, Peixi 1,3,4,5,6; Quan, Kai 1,3,4,5,6; Li, Sichen 1,3,4,5,6; Liu, Yingjun 1,3,4,5,6; Zhu, Wei 1,3,4,5,6; Du, Jiulin2,7,8
	2024-09-01
发表期刊	CARDIOVASCULAR RESEARCH
ISSN	0008-6363
EISSN	1755-3245
发表状态	已发表
DOI	10.1093/cvr/cvae186
摘要	["Aims While previous single-cell RNA sequencing (scRNA-seq) studies have attempted to dissect intracranial aneurysm (IA), the primary molecular mechanism for IA pathogenesis remains unknown. Here, we uncovered the alterations of cellular compositions, especially the transcriptome changes of vascular endothelial cells (ECs), in human IA.Methods and results We performed scRNA-seq to compare the cell atlas of sporadic IA and the control artery. The transcriptomes of 43 462 cells were profiled for further analysis. In general, IA had increased immune cells (T/NK cells, B cells, myeloid cells, mast cells, neutrophils) and fewer vascular cells (ECs, vascular smooth muscle cells, and fibroblasts). Based on the obtained high-quantity and high-quality EC data, we found genes associated with angiogenesis in ECs from IA patients. By EC-specific expression of candidate genes in vivo, we observed the involvement of angpt2a in causing cerebral vascular abnormality. Furthermore, an IA zebrafish model mimicking the main features of human IA was generated through targeting pdgfrb gene, and knockdown of angpt2a alleviated the vascular dilation in the IA zebrafish model.Conclusion By performing a landscape view of the single-cell transcriptomes of IA and the control artery, we contribute to a deeper understanding of the cellular composition and the molecular changes of ECs in IA. The implication of angiogenic regulator ANGPT2 in IA formation and progression, provides a novel potential therapeutical target for IA interventions.","Graphical Abstract"]
关键词	Single-cell RNA sequencing Intracranial aneurysm Endothelial cell Heterogeneity
URL	查看原文
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China["82330039","82171311","82171314","82271339","82201466"] ; Shanghai Excellent Academic Leaders Program[21XD1400600] ; Special Clinical Research Project in Health Industry of Shanghai Municipal Health Commission[20224Y0072] ; Clinical Research Plan of SHDC["SHDC2020CR2034B","SHDC2020CR4033"] ; Shanghai Science and Technology Commission Project[23ZR1408700] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX01] ; CAMS Innovation Fund for Medical Sciences (CIFMS)[2019-I2M-5-008] ; National Key R&D Program of China[2019YFA0801603]
WOS研究方向	Cardiovascular System & Cardiology
WOS类目	Cardiac & Cardiovascular Systems
WOS记录号	WOS:001313891900001
出版者	OXFORD UNIV PRESS
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/427467
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_杜久林组
通讯作者	Zhu, Wei; Du, Jiulin
作者单位	1.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Neurosurg, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China 2.Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techno, State Key Lab Neurosci, 320 Yueyang Rd, Shanghai 200031, Peoples R China 3.Natl Ctr Neurol Disorders, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China 4.Shanghai Key Lab Brain Funct & Restorat & Neural R, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China 5.Fudan Univ, Neurosurg Inst, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China 6.Shanghai Clin Med Ctr Neurosurg, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China 7.Univ Chinese Acad Sci, Inst Neurosci, 19A Yu-Quan Rd, Beijing 100049, Peoples R China 8.ShanghaiTech Univ, Sch Life Sci & Technol, 319 Yue-Yang Rd, Shanghai 200031, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yu, Guo,Li, Jia,Zhang, Hongfei,et al. Single-cell analysis reveals the implication of vascular endothelial cell-intrinsic ANGPT2 in human intracranial aneurysm[J]. CARDIOVASCULAR RESEARCH,2024.
APA	Yu, Guo.,Li, Jia.,Zhang, Hongfei.,Zi, Huaxing.,Liu, Mingjian.,...&Du, Jiulin.(2024).Single-cell analysis reveals the implication of vascular endothelial cell-intrinsic ANGPT2 in human intracranial aneurysm.CARDIOVASCULAR RESEARCH.
MLA	Yu, Guo,et al."Single-cell analysis reveals the implication of vascular endothelial cell-intrinsic ANGPT2 in human intracranial aneurysm".CARDIOVASCULAR RESEARCH (2024).