Critical role of cell competition in gliomagenesis
Jiang Y, Ahn R, Huang A, Gonzalez PP, Kim J, Zhang G, Liu Z, He Z, Dudley L, Patel KS, Dzhivhuho GA, Crowl S, Przanowski P, Camacho LQ, Hao S, Zeng J, Hippenmeyer S, Fallahi-Sichani M, Janes KA, Naegle KM, Hammarskjold M-L, Goldman SA, Kornblum HI, Yao M, White F, Zong H. 2026. Critical role of cell competition in gliomagenesis. bioRxiv, 10.64898/2026.01.15.699808.
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Author
Jiang, Ying;
Ahn, Ryuhjin;
Huang, Arthur;
Gonzalez, Phillippe P.;
Kim, Jungeun;
Zhang, Guoxin;
Liu, Zihao;
He, Zhenqiang;
Dudley, Lindsey;
Patel, Kunal S.;
Dzhivhuho, Godfrey A.;
Crowl, Sam
All
All
Department
Abstract
Malignant glioma is incurable. Using a mouse genetic mosaic system to generate sporadic Trp53,Nf1-null OPCs, we previously identified oligodendrocyte precursor cell (OPC) as a cell-of-origin of glioma. Here, we report that pre-malignant Trp53,Nf1-null OPCs outcompete wildtype counterparts during their expansion. Blocking competition by mutating/strengthening wildtype OPCs impeded both pre-malignant progression and malignant expansion of glioma.
“In-tissue” phosphoproteomic profiling revealed an enrichment of phosphopeptides related to RNA splicing and protein translation at the peak of cell competition, suggesting that competitiveness may stem from unique protein species. Among candidates was mTORC1, whose pharmacological inhibition or genetic disruption resulted in a loss of competitiveness in our mouse model. Finally, analysis of patient biopsies and interrogating the role of individual gliomagenic mutations in OPC competition supported its relevance in human gliomas. Together, these findings identified the driving role of competitive interactions among OPCs in gliomagenesis, and suggest unconventional therapeutic strategies to target this process.
Publishing Year
Date Published
2026-01-16
Journal Title
bioRxiv
Acknowledgement
We thank Dr. Wenjie Liu for providing critical feedback on the manuscript. We also thank Dr.
Pat Pramoonjago at the Biorepository and Tissue Research Facility, and Hope Davis at the
vivarium for their assistance on the project. These Core Facilities are supported by UVA Cancer
Center grant #P30-CA044579. We are grateful to Dr. Jonathan A. Epstein for providing the
Nf1GRD/+ mouse strain (https://pubmed.ncbi.nlm.nih.gov/26460546/). This work was partly
supported by the National Institute of Neurological Diseases and Stroke R21 NS125479-01A1
(H.Z.), American Cancer Society Institutional Research Grant to the University of Virginia
(Y.J.), the National Natural Science Foundation of China #82072787 (M.Y.), the National
Cancer Institute U54 CA238114 (F.W.), U01 CA284193 (K.M.N.), and U54 CA274499 (K.A.J.,
M.F-S.), the National institute of General Medical Sciences R35 GM133404 (M.F-S.), the Dr.
Miriam and Sheldon G. Adelson Medical Research Foundation (H.I.K., S.A.G.), the National
Center for Advancing Translational Sciences KL2TR001882 (K.S.P.), Tower Cancer Career Development Grant (K.S.P.), McKnight Neurobiology of Brain Disorders Grant (K.S.P.). The
content is solely the responsibility of the authors and does not necessarily represent the official
views of the National Institutes of Health. Illustrations in this manuscript were created with
BioRender (BioRender.com).
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Cite this
Jiang Y, Ahn R, Huang A, et al. Critical role of cell competition in gliomagenesis. bioRxiv. 2026. doi:10.64898/2026.01.15.699808
Jiang, Y., Ahn, R., Huang, A., Gonzalez, P. P., Kim, J., Zhang, G., … Zong, H. (2026). Critical role of cell competition in gliomagenesis. bioRxiv. https://doi.org/10.64898/2026.01.15.699808
Jiang, Ying, Ryuhjin Ahn, Arthur Huang, Phillippe P. Gonzalez, Jungeun Kim, Guoxin Zhang, Zihao Liu, et al. “Critical Role of Cell Competition in Gliomagenesis.” BioRxiv, 2026. https://doi.org/10.64898/2026.01.15.699808.
Y. Jiang et al., “Critical role of cell competition in gliomagenesis,” bioRxiv. 2026.
Jiang Y, Ahn R, Huang A, Gonzalez PP, Kim J, Zhang G, Liu Z, He Z, Dudley L, Patel KS, Dzhivhuho GA, Crowl S, Przanowski P, Camacho LQ, Hao S, Zeng J, Hippenmeyer S, Fallahi-Sichani M, Janes KA, Naegle KM, Hammarskjold M-L, Goldman SA, Kornblum HI, Yao M, White F, Zong H. 2026. Critical role of cell competition in gliomagenesis. bioRxiv, 10.64898/2026.01.15.699808.
Jiang, Ying, et al. “Critical Role of Cell Competition in Gliomagenesis.” BioRxiv, 2026, doi:10.64898/2026.01.15.699808.
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