MODL-45. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL

• DOI: 10.1093/neuonc/noad179.1196
• Publication Date: 2023-11-11T23:37:05Z
• Authors: Lulu Xing; Hope Lancero; Dolores Hambardzu...; Tobias Merson; Claudia Petritsch
• Keywords: Cell type

Abstract In the central nervous system (CNS), gliomas represent almost 50% of all pediatric tumors and due to their complex histological biological heterogeneity, aggressive standard treatment consisting surgery chemoradiotherapy remains ineffective. As a result, more biologically based therapies are urgently needed this requires deeper knowledge etiology biology gliomas, which can arise from oligodendrocyte progenitor cells (OPCs). OPCs most proliferative cell type in CNS, upon oncogenic mutations OPCs, they exhibit defective asymmetric divisions with concomitant increase symmetrical renewal, leading aberrant growth prior malignancy. Although OPC-like frequently found human glioma significantly contribute tumor heterogeneity malignancy, how resident tumor-infiltrating functionally integrate into networks within microenvironment unknown. However, order address critical gap field, novel mouse model conditional OPC ablation must be used overcome methodological challenges current approaches that often result partial transient ablation, limits our understanding long-term function OPCs. Here, we have successfully developed pharmacogenetic eliminating 98.6% throughout brain for up 12 days post ablation. This complete combined intracranial injection reveal longitudinal spatial functional roles necessity context. Understanding OPC-tumor crosstalk by using state-of-the-art approach at both cellular molecular levels will significant clinical implications improving patients gliomas.