Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier

被引：15

作者：

Xie, Yuan ^{[1
,2
]}

Yang, Fan ^{[3
]}

He, Liqun ^{[3
]}

Huang, Hua ^{[3
]}

Chao, Min ^{[4
]}

Cao, Haiyan ^{[4
]}

Hu, Yaqin ^{[4
]}

Fan, Zhicheng ^{[4
]}

Zhai, Yaohong ^{[1
]}

Zhao, Wenjian ^{[4
]}

Liu, Xian ^{[1
]}

Zhao, Ruozhu ^{[1
]}

Xiao, Bing ^{[1
]}

Shi, Xinxin ^{[1
]}

Luo, Yuancheng ^{[5
]}

Yin, Jinlong ^{[6
,7
]}

Feng, Dayun ^{[4
]}

Hugnot, Jean-Philippe ^{[2
,8
]}

Muhl, Lars ^{[3
,9
]}

Dimberg, Anna ^{[3
]}

Betsholtz, Christer ^{[3
,9
]}

Zhang, Yanyu ^{[4
,10
]}

Wang, Liang ^{[4
]}

Zhang, Lei ^{[1
,2
]}

机构：

[1] Shaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Natl Engn Lab Resource Developing Endangered Chine, Xian 710119, Peoples R China

[2] Jinfeng Lab, Chongqing 401329, Peoples R China

[3] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Rudbeck Lab, SE-75185 Uppsala, Sweden

[4] Fourth Mil Med Univ, Tangdu Hosp, Dept Neurosurg, 569 Xinsi Rd, Xian 710038, Peoples R China

[5] Imperial Coll London, Fac Med, Dept Immunol & Inflammat, Commonwealth Bldg,Du Cane Rd, London W12 0NN, England

[6] Henan Univ, Sch Life Sci, Henan Key Lab Brain Targeted Bionanomed, Kaifeng 475004, Henan, Peoples R China

[7] Henan Univ, Sch Pharm, Kaifeng, Henan, Peoples R China

[8] Univ Montpellier, Inst Genom Fonct, CNRS, INSERM, Montpellier, France

[9] Karolinska Inst, Dept Med Huddinge, S-14157 Huddinge, Sweden

[10] Fourth Mil Med Univ, Xijing Hosp, Dept Neurosurg, Xian 710032, Peoples R China

来源：

NEURON | 2024年 / 112卷 / 18期

基金：

中国国家自然科学基金;

关键词：

PERICYTES; VESSELS; ATLAS; ARF; CNS;

D O I：

10.1016/j.neuron.2024.07.026

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The blood-brain barrier (BBB) serves as a crucial vascular specialization, shielding and nourishing brain neurons and glia while impeding drug delivery. Here, we conducted single-cell mRNA sequencing of human cerebrovascular cells from 13 surgically resected glioma samples and adjacent normal brain tissue. The transcriptomes of 103,230 cells were mapped, including 57,324 endothelial cells (ECs) and 27,703 mural cells (MCs). Both EC and MC transcriptomes originating from lower-grade glioma were indistinguishable from those of normal brain tissue, whereas transcriptomes from glioblastoma (GBM) displayed a range of abnormalities. Among these, we identified LOXL2-dependent collagen modification as a common GBM-dependent trait and demonstrated that inhibiting LOXL2 enhanced chemotherapy efficacy in both murine and human patient-derived xenograft (PDX) GBM models. Our comprehensive single-cell RNA sequencing-based molecular atlas of the human BBB, coupled with insights into its perturbations in GBM, holds promise for guiding future investigations into brain health, pathology, and therapeutic strategies.

引用

页码：3089 / 3105.e7

页数：25

共 72 条

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