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.

中文翻译：

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人血脑屏障和神经胶质瘤血肿瘤屏障的单细胞解剖


血脑屏障（BBB）是重要的血管特化，保护和滋养大脑神经元和神经胶质细胞，同时阻碍药物输送。在这里，我们对来自 13 个手术切除的神经胶质瘤样本和邻近正常脑组织的人脑血管细胞进行了单细胞 mRNA 测序。绘制了 103,230 个细胞的转录组图谱，其中包括 57,324 个内皮细胞 (EC) 和 27,703 个壁细胞 (MC)。来自低级别胶质瘤的 EC 和 MC 转录组与正常脑组织的转录组无法区分，而来自胶质母细胞瘤 (GBM) 的转录组则显示出一系列异常。其中，我们将 LOXL2 依赖性胶原蛋白修饰确定为常见的 GBM 依赖性特征，并证明抑制 LOXL2 可增强小鼠和人类患者来源的异种移植 (PDX) GBM 模型中的化疗疗效。我们基于单细胞 RNA 测序的人类 BBB 分子图谱，加上对其在 GBM 中扰动的深入了解，有望指导未来对大脑健康、病理学和治疗策略的研究。