Single-Cell Transcriptomics of Glioblastoma Reveals Pericytes Contributing to Blood–Brain Tumor Barrier and Tumor Progression

Abstract

Abstract Background:Pericytes compose blood–brain barrier (BBB) and may affects the blood-brain tumor barrier function (BBTB) in glioblastoma (GBM), which eventually affect chemotherapy efficiency and tumor progression of the disease. However, the expression signatures and detailed effect of these pericyte are still unclear. We aimed to identify these pericytes affecting BBTB in GBM, and to explore their clinical effect and underlying functions. Methods: Pericytes in GBM were identified from single-cell RNA sequencing (scRNA-seq) da ta from nine GBM samples by hallmarks and expression signatures of pericytes from previous researches, and cell cluster functional enrichments were also used in identification. CellPhoneDB were used to explore interactions between target pericyte and other cells. One in-house glioma clinical cohort was collected and included for survival analysis. CGGA, REMBRANDT, and GSE16011 GBM cohorts were used to develop and validate a tumor pericyte risk score (TPRS) for prognosis prediction. Results: This study demonstrated that a group of pericytes concerning BBTB function exist in GBM, and PTH1R may be a specific biomarker for them. The pericytes of BBTB function interact with other cell in GBM mainly through extracellular matrix (ECM)-integrin signaling pathways. Also, when comparing with normal pericytes, pericytes in GBM has up-regulation of several ECM gene networks (THY1, COL3A1, COL4A1, TIMP1, FN1 etc.) related to poor prognosis and basement membrane formation. TPRS based on those differentially expressed genes (DEGs) has significant predictive value in GBM patients. Conclusions:Pericytes of BBTB function in GBM exist and PTH1R potentially serving as a hallmark for them. These cells have close functional relationships with BBTB and ECM-integrin signing pathways, and may have predictive value for GBM patients.