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Series GSE230389 Query DataSets for GSE230389
Status Public on Dec 01, 2023
Title Single cell data from IDH mutant astroxytoma and IDH wildtype GBM tumor specimen
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their functional role in gliomagenesis and their potential as treatment targets. To identify therapeutically targetable opportunities among aGPCR family members in an unbiased fashion, we analyzed expression levels of all aGPCRs in GBM and non-neoplastic brain tissue. Using bulk and single cell transcriptomic and proteomic data, we show that CD97 (ADGRE5), an aGPCR previously implicated in GBM pathogenesis, is the most promising aGPCR target in GBM, by virtue of its abundance in all GBM tumors and its de novo expression profile in GBM compared to normal brain tissue and neural progenitors. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cells (PDGC) in vitro and in vivo. Transcriptomic and metabolomic data from PDGCs suggest that CD97 promotes glycolytic metabolism. The oncogenic and metabolic effects of CD97 are mediated by the MAPK pathway. Activation of MAPK signaling depends on phosphorylation of the cytosolic C-terminus of CD97 and recruitment of -arrestin. Using single-cell RNA-sequencing and biochemical assays, we demonstrate that THY1/CD90 is the most likely CD97 ligand in GBM. Lastly, we show that targeting of GBM cells with an anti-CD97 antibody-drug conjugate in vitro selectively kills tumor cells but not human astrocytes or neural stem cells. Our studies identify CD97 as an important regulator of tumor metabolism in GBM, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target CD97 in GBM.
Overall design Glioma specimen are flash frozen and single cell RNAsequencing and ATAC sequencing
The sample was then processed as described in the “10X Genomics Nuclei Isolation from Complex Tissues for Single Cell Multiome ATAC + GEX Sequencing Demonstrated Protocol CG000375 Rev B”
Contributor(s) Ravn-Boess N, Placantonakis D
Citation(s) 37938973
Submission date Apr 24, 2023
Last update date Feb 15, 2024
Contact name Niklas Ravn-Boess
Organization name NYU Langone
Street address 550 1st Avenue
City New York
State/province NY
ZIP/Postal code 10016
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (4)
GSM7221332 IDH wildtype GBM, scRNAseq
GSM7221333 IDH wildtype GBM, scATACseq
GSM7221334 IDH mutant astrocytoma, scRNAseq
BioProject PRJNA961045

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE230389_RAW.tar 6.8 Gb (http)(custom) TAR (of MTX, TBI, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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