High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses
- 1Stanford University
Abstract
The mechanisms regulating glioma cell death are poorly understood. Here, we developed a high-throughput method to study cell death in patient-derived glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) spheroids. Using this method, we systematically profiled how extracellular ligands modulate compound-induced cell death. We find that bone morphogenetic protein 2 (BMP2) and BMP4 potently rewire cell death sensitivity. These ligands suppress killing by standard-of-care DNA alkylating agents and kinase inhibitors by inhibiting cell cycle progression. Simultaneously, BMP2/4 prime spheroids for lipid-dependent necrosis (LiDN), a palmitate-dependent form of non-apoptotic cell death that can be triggered by the clinical drug candidate tegavivint. Activating mutations in the BMP receptor ACVR1, found in ~25% of DIPG tumors, are sufficient to prime cells for LiDN in the absence of BMP ligand. Together, these findings identify a cell death switch that can be activated in glioma cells by BMP signaling.
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BibTeX
@misc{lee2026highthroughput,
title = {{High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses}},
author = {W. C. Lee and J. J. Salinas and A. Gautam and D. Cadet and M. A. Banu and D. A. Nathanson and S. J. Dixon},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750657},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750657v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses
AU - W. C. Lee
AU - J. J. Salinas
AU - A. Gautam
AU - D. Cadet
AU - M. A. Banu
AU - D. A. Nathanson
AU - S. J. Dixon
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750657
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750657v1
AB - The mechanisms regulating glioma cell death are poorly understood. Here, we developed a high-throughput method to study cell death in patient-derived glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) spheroids. Using this method, we systematically profiled how extracellular ligands modulate compound-induced cell death. We find that bone morphogenetic protein 2 (BMP2) and BMP4 potently rewire cell death sensitivity. These ligands suppress killing by standard-of-care DNA alkylating agents and kinase inhibitors by inhibiting cell cycle progression. Simultaneously, BMP2/4 prime spheroids for lipid-dependent necrosis (LiDN), a palmitate-dependent form of non-apoptotic cell death that can be triggered by the clinical drug candidate tegavivint. Activating mutations in the BMP receptor ACVR1, found in ~25% of DIPG tumors, are sufficient to prime cells for LiDN in the absence of BMP ligand. Together, these findings identify a cell death switch that can be activated in glioma cells by BMP signaling.
ER -