Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier.
Neuron
; 112(18): 3089-3105.e7, 2024 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-39191260
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Barrera Hematoencefálica
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Análisis de la Célula Individual
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Glioma
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article