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BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL

In the central nervous system (CNS), gliomas represent almost 50% of all pediatric tumors and due to their complex histological and biological heterogeneity, aggressive standard treatment consisting of surgery and chemoradiotherapy remains ineffective. As a result, more biologically based therapies...

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Detalles Bibliográficos
Autores principales: Xing, Lulu, Merson, Tobias, Petritsch, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260058/
http://dx.doi.org/10.1093/neuonc/noad073.025
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author Xing, Lulu
Merson, Tobias
Petritsch, Claudia
author_facet Xing, Lulu
Merson, Tobias
Petritsch, Claudia
author_sort Xing, Lulu
collection PubMed
description In the central nervous system (CNS), gliomas represent almost 50% of all pediatric tumors and due to their complex histological and biological heterogeneity, aggressive standard treatment consisting of surgery and chemoradiotherapy remains ineffective. As a result, more biologically based therapies are urgently needed, and this requires a deeper knowledge of the etiology and biology of gliomas and the tumor microenvironment. Oligodendrocyte progenitor cells (OPCs) are a potential origin of human gliomas (as suggested by studies in genetically engineered mouse models) and human OPC-like tumor cells contribute to tumor heterogeneity and malignancy. Resident (non-neoplastic) OPCs have been found to intermix with glioma cells and proliferate within the tumor microenvironment. The significance of the interactions of resident OPCs and glioma cells remains unknown. We hypothesize that resident OPCs functionally integrate into the tumor cell network and affect tumor properties. We have generated a novel mouse model of conditional OPC ablation to overcome methodological challenges of most current approaches that often result in partial and transient OPC ablation, which limits our understanding of long-term function of OPCs. Here in our study, we have successfully developed a novel pharmacogenetic model of conditional OPC ablation, eliminating 98.6% of all OPCs throughout the mouse brain for up to 12 days post ablation. In the future, we plan to combine the mouse model of complete OPC ablation with orthotopic glioma models to reveal the longitudinal and spatial functional roles and the necessity for resident OPCs in the tumor context. Understanding the OPC-tumor cell crosstalk by using our state-of-the-art approach at both cellular and molecular levels will have significant clinical implications for improving treatment for patients with pediatric gliomas.
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spelling pubmed-102600582023-06-13 BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL Xing, Lulu Merson, Tobias Petritsch, Claudia Neuro Oncol Final Category: Basic Biology/Stem Cells/Models - BIOL In the central nervous system (CNS), gliomas represent almost 50% of all pediatric tumors and due to their complex histological and biological heterogeneity, aggressive standard treatment consisting of surgery and chemoradiotherapy remains ineffective. As a result, more biologically based therapies are urgently needed, and this requires a deeper knowledge of the etiology and biology of gliomas and the tumor microenvironment. Oligodendrocyte progenitor cells (OPCs) are a potential origin of human gliomas (as suggested by studies in genetically engineered mouse models) and human OPC-like tumor cells contribute to tumor heterogeneity and malignancy. Resident (non-neoplastic) OPCs have been found to intermix with glioma cells and proliferate within the tumor microenvironment. The significance of the interactions of resident OPCs and glioma cells remains unknown. We hypothesize that resident OPCs functionally integrate into the tumor cell network and affect tumor properties. We have generated a novel mouse model of conditional OPC ablation to overcome methodological challenges of most current approaches that often result in partial and transient OPC ablation, which limits our understanding of long-term function of OPCs. Here in our study, we have successfully developed a novel pharmacogenetic model of conditional OPC ablation, eliminating 98.6% of all OPCs throughout the mouse brain for up to 12 days post ablation. In the future, we plan to combine the mouse model of complete OPC ablation with orthotopic glioma models to reveal the longitudinal and spatial functional roles and the necessity for resident OPCs in the tumor context. Understanding the OPC-tumor cell crosstalk by using our state-of-the-art approach at both cellular and molecular levels will have significant clinical implications for improving treatment for patients with pediatric gliomas. Oxford University Press 2023-06-12 /pmc/articles/PMC10260058/ http://dx.doi.org/10.1093/neuonc/noad073.025 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Basic Biology/Stem Cells/Models - BIOL
Xing, Lulu
Merson, Tobias
Petritsch, Claudia
BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
title BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
title_full BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
title_fullStr BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
title_full_unstemmed BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
title_short BIOL-06. UNDERSTANDING OLIGODENDROCYTE PROGENITOR CELL CONTRIBUTION TO GLIOMAGENESIS USING A NOVEL PHARMACOGENETIC ABLATION TOOL
title_sort biol-06. understanding oligodendrocyte progenitor cell contribution to gliomagenesis using a novel pharmacogenetic ablation tool
topic Final Category: Basic Biology/Stem Cells/Models - BIOL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260058/
http://dx.doi.org/10.1093/neuonc/noad073.025
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