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The white matter is a pro-differentiative niche for glioblastoma
Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma stem cells are maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we iden...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042097/ https://www.ncbi.nlm.nih.gov/pubmed/33846316 http://dx.doi.org/10.1038/s41467-021-22225-w |
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author | Brooks, Lucy J. Clements, Melanie P. Burden, Jemima J. Kocher, Daniela Richards, Luca Devesa, Sara Castro Zakka, Leila Woodberry, Megan Ellis, Michael Jaunmuktane, Zane Brandner, Sebastian Morrison, Gillian Pollard, Steven M. Dirks, Peter B. Marguerat, Samuel Parrinello, Simona |
author_facet | Brooks, Lucy J. Clements, Melanie P. Burden, Jemima J. Kocher, Daniela Richards, Luca Devesa, Sara Castro Zakka, Leila Woodberry, Megan Ellis, Michael Jaunmuktane, Zane Brandner, Sebastian Morrison, Gillian Pollard, Steven M. Dirks, Peter B. Marguerat, Samuel Parrinello, Simona |
author_sort | Brooks, Lucy J. |
collection | PubMed |
description | Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma stem cells are maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte lineage competency. Tumour cells in contact with white matter acquire pre-oligodendrocyte fate, resulting in decreased proliferation and invasion. Differentiation is a response to white matter injury, which is caused by tumour infiltration itself in a tumoursuppressive feedback loop. Mechanistically, tumour cell differentiation is driven by selective white matter upregulation of SOX10, a master regulator of normal oligodendrogenesis. SOX10 overexpression or treatment with myelination-promoting agents that upregulate endogenous SOX10, mimic this response, leading to niche-independent pre-oligodendrocyte differentiation and tumour suppression in vivo. Thus, glioblastoma recapitulates an injury response and exploiting this latent programme may offer treatment opportunities for a subset of patients. |
format | Online Article Text |
id | pubmed-8042097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80420972021-04-30 The white matter is a pro-differentiative niche for glioblastoma Brooks, Lucy J. Clements, Melanie P. Burden, Jemima J. Kocher, Daniela Richards, Luca Devesa, Sara Castro Zakka, Leila Woodberry, Megan Ellis, Michael Jaunmuktane, Zane Brandner, Sebastian Morrison, Gillian Pollard, Steven M. Dirks, Peter B. Marguerat, Samuel Parrinello, Simona Nat Commun Article Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma stem cells are maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte lineage competency. Tumour cells in contact with white matter acquire pre-oligodendrocyte fate, resulting in decreased proliferation and invasion. Differentiation is a response to white matter injury, which is caused by tumour infiltration itself in a tumoursuppressive feedback loop. Mechanistically, tumour cell differentiation is driven by selective white matter upregulation of SOX10, a master regulator of normal oligodendrogenesis. SOX10 overexpression or treatment with myelination-promoting agents that upregulate endogenous SOX10, mimic this response, leading to niche-independent pre-oligodendrocyte differentiation and tumour suppression in vivo. Thus, glioblastoma recapitulates an injury response and exploiting this latent programme may offer treatment opportunities for a subset of patients. Nature Publishing Group UK 2021-04-12 /pmc/articles/PMC8042097/ /pubmed/33846316 http://dx.doi.org/10.1038/s41467-021-22225-w Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Brooks, Lucy J. Clements, Melanie P. Burden, Jemima J. Kocher, Daniela Richards, Luca Devesa, Sara Castro Zakka, Leila Woodberry, Megan Ellis, Michael Jaunmuktane, Zane Brandner, Sebastian Morrison, Gillian Pollard, Steven M. Dirks, Peter B. Marguerat, Samuel Parrinello, Simona The white matter is a pro-differentiative niche for glioblastoma |
title | The white matter is a pro-differentiative niche for glioblastoma |
title_full | The white matter is a pro-differentiative niche for glioblastoma |
title_fullStr | The white matter is a pro-differentiative niche for glioblastoma |
title_full_unstemmed | The white matter is a pro-differentiative niche for glioblastoma |
title_short | The white matter is a pro-differentiative niche for glioblastoma |
title_sort | white matter is a pro-differentiative niche for glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042097/ https://www.ncbi.nlm.nih.gov/pubmed/33846316 http://dx.doi.org/10.1038/s41467-021-22225-w |
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