Work

Transcription factors ASCL1 and OLIG2 drive glioblastoma initiation and co-regulate tumor cell types and migration

Year: 2024

Type: article

Abstract: Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex genetic alterations. The basic-helix-loop-helix (bHLH) transcription factors ASCL1 and OLIG2 are dynamically co-expressed in GBMs; however, their combinatorial roles in regulating the plasticity and heterogeneity of GBM cells are unclear. Here, we show that induction of somatic mutations in subventricular zone (SVZ) progenitor cells leads to the dysregulation of ASCL1 and OLIG2, which then function redundantly and are required for brain tumor formation in a mouse model of GBM. Subsequently, the binding of ASCL1 and OLIG2 to each other's loci and to downstream target genes then determines the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in specifying highly migratory neural stem cell (NSC)/astrocyte-like tumor cell types, which are marked by upregulation of ribosomal protein, oxidative phosphorylation, cancer metastasis, and therapeutic resistance genes.

Source: Nature Communications

DOI: 10.1038/s41467-024-54750-9

Authors: Bianca L. Myers, Kathryn J. Brayer, Luis E. Paez-Beltran, Estrella Villicana, Matthew S. Keith, Hideaki Suzuki, Jessie Newville, Rebekka H. Anderson, Yunee Lo, Conner M. Mertz, Rahul K. Kollipara, Mark D. Borromeo, Q. Richard Lu, Robert M. Bachoo, Jane E. Johnson, Tou Yia Vue

Institutions: University of New Mexico Health Sciences Center, UNM Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Cincinnati Children's Hospital Medical Center, University of New Mexico

Language: English

Topic: Glioma Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,790

Funders: U.S. Department of Health and Human Services, Cancer Prevention and Research Institute of Texas, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke

Awards: G1242030391, University of New Mexico (UNM) Center for Brain Recovery and Repair, G1773891675, G1849608474, G185023344, G2686577794, G3450108671, G3467610764, G4561770348, G5696203896, G6728359409, Transcriptional control of OPC fate specification and homing to gray matter and white matter in the CNS, University of New Mexico Cancer Center Support, G7810090824, G8112046376, Requirement for Ascl1 in Gliomagenesis, University of Colorado Cancer Center Support Grant, Alcohol Research Training in Neurosciences

OpenAlex ID: W4404795545

FWCI: 7.63

Cites: 126

Cited by: 33

Related to: 10