Cargando…

OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma

Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most common primary brain tumor in adults. GBM has the poorest prognosis and no efficient cure to date due to diffusive growth into the surrounding brain, preventing complete surgical resection and leading to ine...

Descripción completa

Detalles Bibliográficos
Autores principales: Dzwigonska, Monika, Mieczkowski, Jakub, Pilanc, Paulina, Cyranowski, Salwador, Kominek, Agata, Piwocka, Katarzyna, Kaminska, Bozena, Leszczynska, Katarzyna B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255465/
http://dx.doi.org/10.1093/noajnl/vdab070.053
_version_ 1783717911853006848
author Dzwigonska, Monika
Mieczkowski, Jakub
Pilanc, Paulina
Cyranowski, Salwador
Kominek, Agata
Piwocka, Katarzyna
Kaminska, Bozena
Leszczynska, Katarzyna B
author_facet Dzwigonska, Monika
Mieczkowski, Jakub
Pilanc, Paulina
Cyranowski, Salwador
Kominek, Agata
Piwocka, Katarzyna
Kaminska, Bozena
Leszczynska, Katarzyna B
author_sort Dzwigonska, Monika
collection PubMed
description Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most common primary brain tumor in adults. GBM has the poorest prognosis and no efficient cure to date due to diffusive growth into the surrounding brain, preventing complete surgical resection and leading to inevitable tumor relapse. Tumor microenvironment (TME) of GBM contains brain-residing microglia and bone-marrow derived macrophages (collectively known as glioma-associated microglia/macrophages, GAMs) that constitute up to 30% of the tumor mass and promote tumor invasion. Hypoxia (a shortage of oxygen) is a key factor in tumor progression of GBM as it can globally and rapidly alter the gene expression, induce cancer cell invasiveness, stemness and lead to therapy resistance. Hypoxia can enhance the pro-tumorigenic function of GAMs, e.g. by inducing expression of cytokines and cell surface receptors both in GAMs and glioma cells, but little is known about chromatin alterations of GBM under hypoxia. Since regulation of expression of such molecules could depend on the epigenetic alterations, we hypothesize that hypoxia may potently alter the chromatin accessibility and functions of GAMs and glioma cells. We determine the genome-wide changes in chromatin accessibility in GAMs and glioma cells in response to hypoxic stress using single-cell Pi-ATAC-seq (Protein-indexed Assay of Transposase Accessible Chromatin with sequencing), which allows simultaneous genome-wide assessment of chromatin accessibility and expression of intracellular protein markers in single cells, allowing faithful selection of hypoxic and non-hypoxic cells. Secondly, we are employing an oxygen-dependent co-culture model in vitro to study the mechanisms of chromatin alterations in GAMs and glioma cells under controlled hypoxic conditions and test how these changes depend on the glioma - GAMs cross-communication. In summary, we characterize the interactions between innate immune cells and glioma cells by looking at their chromatin alterations under hypoxia. Supported by the National Science Center grant (Poland) 2019/33/B/NZ1/01556 (KBL).
format Online
Article
Text
id pubmed-8255465
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-82554652021-07-06 OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma Dzwigonska, Monika Mieczkowski, Jakub Pilanc, Paulina Cyranowski, Salwador Kominek, Agata Piwocka, Katarzyna Kaminska, Bozena Leszczynska, Katarzyna B Neurooncol Adv Supplement Abstracts Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most common primary brain tumor in adults. GBM has the poorest prognosis and no efficient cure to date due to diffusive growth into the surrounding brain, preventing complete surgical resection and leading to inevitable tumor relapse. Tumor microenvironment (TME) of GBM contains brain-residing microglia and bone-marrow derived macrophages (collectively known as glioma-associated microglia/macrophages, GAMs) that constitute up to 30% of the tumor mass and promote tumor invasion. Hypoxia (a shortage of oxygen) is a key factor in tumor progression of GBM as it can globally and rapidly alter the gene expression, induce cancer cell invasiveness, stemness and lead to therapy resistance. Hypoxia can enhance the pro-tumorigenic function of GAMs, e.g. by inducing expression of cytokines and cell surface receptors both in GAMs and glioma cells, but little is known about chromatin alterations of GBM under hypoxia. Since regulation of expression of such molecules could depend on the epigenetic alterations, we hypothesize that hypoxia may potently alter the chromatin accessibility and functions of GAMs and glioma cells. We determine the genome-wide changes in chromatin accessibility in GAMs and glioma cells in response to hypoxic stress using single-cell Pi-ATAC-seq (Protein-indexed Assay of Transposase Accessible Chromatin with sequencing), which allows simultaneous genome-wide assessment of chromatin accessibility and expression of intracellular protein markers in single cells, allowing faithful selection of hypoxic and non-hypoxic cells. Secondly, we are employing an oxygen-dependent co-culture model in vitro to study the mechanisms of chromatin alterations in GAMs and glioma cells under controlled hypoxic conditions and test how these changes depend on the glioma - GAMs cross-communication. In summary, we characterize the interactions between innate immune cells and glioma cells by looking at their chromatin alterations under hypoxia. Supported by the National Science Center grant (Poland) 2019/33/B/NZ1/01556 (KBL). Oxford University Press 2021-07-05 /pmc/articles/PMC8255465/ http://dx.doi.org/10.1093/noajnl/vdab070.053 Text en © The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Supplement Abstracts
Dzwigonska, Monika
Mieczkowski, Jakub
Pilanc, Paulina
Cyranowski, Salwador
Kominek, Agata
Piwocka, Katarzyna
Kaminska, Bozena
Leszczynska, Katarzyna B
OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
title OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
title_full OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
title_fullStr OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
title_full_unstemmed OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
title_short OTME-2. Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
title_sort otme-2. regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
topic Supplement Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255465/
http://dx.doi.org/10.1093/noajnl/vdab070.053
work_keys_str_mv AT dzwigonskamonika otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT mieczkowskijakub otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT pilancpaulina otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT cyranowskisalwador otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT kominekagata otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT piwockakatarzyna otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT kaminskabozena otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma
AT leszczynskakatarzynab otme2regulationofchromatinaccessibilityinthehypoxictumormicroenvironmentofglioblastoma