PREreviews of “Spatial multi-omics defines a shared glioblastoma infiltrative signature at the resection margin”

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Spatial multi-omics defines a shared glioblastoma infiltrative signature at the resection margin

by Balagopal Pai, Susana Isabel Ramos, Wan Sze Cheng, Tanvi Joshi, Gabrielle Price, Jessica Tome-Garcia, German Nudelman, Sanjana Shroff, Kristin Beaumont, Yong Raymund, Robert Sebra, Elena Zaslavsky, and Nadejda Mincheva Tsankova

Posted: November 8, 2024
Server: bioRxiv
DOI: 10.1101/2024.11.05.621879

Abstract

Glioblastoma (GBM) remains an untreatable disease. Understanding GBM’s infiltrative biology at the resection margin is limited, despite causing disease recurrence and progression. To address this, we generated a high-throughput single-nucleus (sn)RNA-seq and snATAC-seq multi-omic dataset from six tumors with distinct genomic drivers and combined it with spatial transcriptomics to characterize the unique molecular phenotype of GBM near the margin. By contrasting GBM-specific biology in matching “Core” vs. “Margin” dissections, we define unique, shared “GBM infiltration” and chromatin accessibility signatures near the margin. We prioritizeEGFRas a top differentially expressed and accessible “Margin” marker across GBM subtypes, show its dynamic expression along a core-to-margin infiltration trajectory, and validate its role in migration through CRISPR/Cas9 deletion in two patient-derived models. ChIP-seq studies furthermore corroborate preferential TEAD1 binding at EGFR’s accessible regulatory elements. This validated multi-omic dataset enables further studies into tumor and microenvironment biology in the context of residual GBM disease.

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PREreview by TONY AVRIL et al. of the Proteostasis and Cancer Team INSERM U1242

Authored by TONY AVRIL and 1 other author of the Proteostasis and Cancer Team INSERM U1242

Pre-review of “Spatial multi-omics defines a shared glioblastoma infiltrative signature at the resection margin”
by Tony Avril, Marc Aubry of the Proteostasis and Cancer team INSERM U1242
Proteostasis and Cancer & @omics Teams
INSERM UMR1242 Oncogenesis Stress Signaling
Centre Eugène Marquis, Rennes…

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PREreviews of Spatial multi-omics defines a shared glioblastoma infiltrative signature at the resection margin

1 PREreview