Tmet-01. Lipid Metabolic Programs Define Glioma State Identity, Plasticity and Dependencies
Year: 2024
Type: conference-abstract
Abstract: Gliomas are lethal malignancies comprised of heterogeneous and dynamic subpopulations of cell states resembling normal neurodevelopmental cell types (radial glia (RG), oligodendrocyte progenitor cell (OPC), neuron progenitor cell (NPC), neuron, etc). While both intrinsic (genetics) and extrinsic (brain environment) cues are coupled to glioma state identity, the functional programs governing glioma cell state and plasticity are unknown. Here we performed a multi-omic interrogation of a large library (n=392) of glioma patient tumors, in vivo orthotopic xenografts and in vitro gliomasphere cultures. Comparisons of matched glioma samples across environments revealed the non-native in vitro environment constrains glioma state diversity specifically enriching for stem-like glioma cell states (RG, immune, vascular). This enrichment was linked to lipid metabolic flexibility, enabling tumors enriched for stem-like states to adapt to various tumor microenvironments. By contrast, “lineage-committed” cell states (OPC, NPC, and neuron) demonstrate restricted lipid metabolism, consequently having a dependence on lipid scavenging from the brain microenvironment for survival. These results connect intra-tumoral heterogeneity and plasticity of glioma to lipid metabolism, leveraging the functional diversity of cellular states to reveal potential therapeutic opportunities.
Source: Neuro-Oncology
Authors: Jenna Minami, Nicholas Bayley, Christopher Tse, Cassidy Andrasz, Dimitri Cadet, Jennifer Salinas, Weihong Yan, Amir Borujerdpur, Linda Liau, Timothy Cloughesy, Kevin Williams, Steven Bensinger, Aparna Bhaduri, Thomas Graeber, David Nathanson
Institution: University of California, Los Angeles
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404236525