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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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”
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| Contributor(s) |
Ravn-Boess N, Placantonakis D |
| Citation(s) |
37938973 |
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| Submission date |
Apr 24, 2023 |
| Last update date |
Feb 15, 2024 |
| Contact name |
Niklas Ravn-Boess |
| Organization name |
NYU Langone
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| Street address |
550 1st Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA961045 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230389_RAW.tar |
6.8 Gb |
(http)(custom) |
TAR (of MTX, TBI, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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