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Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing
Yuan Xie, … , Anna Dimberg, Lei Zhang
Yuan Xie, … , Anna Dimberg, Lei Zhang
Published July 6, 2021
Citation Information: JCI Insight. 2021;6(15):e150861. https://doi.org/10.1172/jci.insight.150861.
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Research Article Vascular biology

Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing

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Abstract

Passage of systemically delivered pharmacological agents into the brain is largely blocked by the blood-brain-barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). Tumor vessels in glioblastoma (GBM), the most common malignant brain tumor in humans, are abnormally permeable, but this phenotype is heterogeneous and may differ between the tumor’s center and invasive front. Here, through single-cell RNA sequencing (scRNA-seq) of freshly isolated ECs from human glioblastoma and paired tumor peripheral tissues, we have constructed a molecular atlas of human brain ECs providing unprecedented molecular insight into the heterogeneity of the human BBB and its molecular alteration in glioblastoma. We identified 5 distinct EC phenotypes representing different states of EC activation and BBB impairment, and associated with different anatomical locations within and around the tumor. This unique data resource provides key information for designing rational therapeutic regimens and optimizing drug delivery.

Authors

Yuan Xie, Liqun He, Roberta Lugano, Yanyu Zhang, Haiyan Cao, Qiyuan He, Min Chao, Boxuan Liu, Qingze Cao, Jianhao Wang, Yang Jiao, Yaqin Hu, Liying Han, Yong Zhang, Hua Huang, Lene Uhrbom, Christer Betsholtz, Liang Wang, Anna Dimberg, Lei Zhang

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Figure 4

ECs in tumor core are distinct from ECs in peripheral brain tissue.

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ECs in tumor core are distinct from ECs in peripheral brain tissue.
(A) ...
(A) Plot of transcription factor activity score estimated by SCENIC to fold change of their expression between ECs in periphery and tumor core. Red/blue dot corresponds to transcription factor activated in ECs in the tumor core or tumor periphery, respectively. (B) Venn diagram illustrating the overlaps of 374 EC-enriched genes with differentially expressed genes between ECs in tumor core and tumor periphery. (C) Heatmap showing differentially expressed EC-enriched genes between ECs in the tumor core and peripheral brain tissue. (D) Bar plots of CAVIN2, HSPG2, and MYO1B among different EC subclusters. (E) IHC staining and quantification of CAVIN2, HSPG2, and MYO1B in human GBM tumor core and paired peripheral brain tissue (CAVIN2, n = 13; HSPG2, n = 13; MYO1B, n = 14). Staining was scored semiquantitatively on scale from 0 to 2 based on proportional of vessels stained (Wilcoxon test, **P < 0.01, ***P < 0.001). Scale bar: 50 μm.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

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