Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/150484 |
Resumo: | Altered metabolic processes contribute to carcinogenesis by modulating proliferation, survival and differentiation. Tumours are composed of different cell populations, with cancer stem-like cells being one of the most prominent examples. This specific pool of cells is thought to be responsible for cancer growth and recurrence and plays a particularly relevant role in glioblastoma (GBM), the most lethal form of primary brain tumours. Here, we have analysed the transcriptome and metabolome of an established GBM cell line (U87) and a patient-derived GBM stem-like cell line (NCH644) exposed to neurosphere or monolayer culture conditions. By integrating transcrip-tome and metabolome data, we identified key metabolic pathways and gene signatures that are associated with stem-like and differentiated states in GBM cells, and demonstrated that neuro-spheres and monolayer cells differ substantially in their metabolism and gene regulation. Further-more, arginine biosynthesis was identified as the most significantly regulated pathway in neuro-spheres, although individual nodes of this pathway were distinctly regulated in the two cellular systems. Neurosphere conditions, as opposed to monolayer conditions, cause a transcriptomic and metabolic rewiring that may be crucial for the regulation of stem-like features, where arginine bio-synthesis may be a key metabolic pathway. Additionally, TCGA data from GBM patients showed significant regulation of specific components of the arginine biosynthesis pathway, providing further evidence for the importance of this metabolic pathway in GBM. |
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Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell linesAltered metabolic processes contribute to carcinogenesis by modulating proliferation, survival and differentiation. Tumours are composed of different cell populations, with cancer stem-like cells being one of the most prominent examples. This specific pool of cells is thought to be responsible for cancer growth and recurrence and plays a particularly relevant role in glioblastoma (GBM), the most lethal form of primary brain tumours. Here, we have analysed the transcriptome and metabolome of an established GBM cell line (U87) and a patient-derived GBM stem-like cell line (NCH644) exposed to neurosphere or monolayer culture conditions. By integrating transcrip-tome and metabolome data, we identified key metabolic pathways and gene signatures that are associated with stem-like and differentiated states in GBM cells, and demonstrated that neuro-spheres and monolayer cells differ substantially in their metabolism and gene regulation. Further-more, arginine biosynthesis was identified as the most significantly regulated pathway in neuro-spheres, although individual nodes of this pathway were distinctly regulated in the two cellular systems. Neurosphere conditions, as opposed to monolayer conditions, cause a transcriptomic and metabolic rewiring that may be crucial for the regulation of stem-like features, where arginine bio-synthesis may be a key metabolic pathway. Additionally, TCGA data from GBM patients showed significant regulation of specific components of the arginine biosynthesis pathway, providing further evidence for the importance of this metabolic pathway in GBM.MDPI20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/150484eng2072-669410.3390/cancers13061327Peixoto, JJanaki-Raman, SSchlicker, LSchmitz, WWalz, SWinkelkotte, AMHerold-Mende, CSoares, PSchulze, ALima, Jinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T15:23:27Zoai:repositorio-aberto.up.pt:10216/150484Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:22:26.962445Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
title |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
spellingShingle |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines Peixoto, J |
title_short |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
title_full |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
title_fullStr |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
title_full_unstemmed |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
title_sort |
Integrated metabolomics and transcriptomics analysis of monolayer and neurospheres from established glioblastoma cell lines |
author |
Peixoto, J |
author_facet |
Peixoto, J Janaki-Raman, S Schlicker, L Schmitz, W Walz, S Winkelkotte, AM Herold-Mende, C Soares, P Schulze, A Lima, J |
author_role |
author |
author2 |
Janaki-Raman, S Schlicker, L Schmitz, W Walz, S Winkelkotte, AM Herold-Mende, C Soares, P Schulze, A Lima, J |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Peixoto, J Janaki-Raman, S Schlicker, L Schmitz, W Walz, S Winkelkotte, AM Herold-Mende, C Soares, P Schulze, A Lima, J |
description |
Altered metabolic processes contribute to carcinogenesis by modulating proliferation, survival and differentiation. Tumours are composed of different cell populations, with cancer stem-like cells being one of the most prominent examples. This specific pool of cells is thought to be responsible for cancer growth and recurrence and plays a particularly relevant role in glioblastoma (GBM), the most lethal form of primary brain tumours. Here, we have analysed the transcriptome and metabolome of an established GBM cell line (U87) and a patient-derived GBM stem-like cell line (NCH644) exposed to neurosphere or monolayer culture conditions. By integrating transcrip-tome and metabolome data, we identified key metabolic pathways and gene signatures that are associated with stem-like and differentiated states in GBM cells, and demonstrated that neuro-spheres and monolayer cells differ substantially in their metabolism and gene regulation. Further-more, arginine biosynthesis was identified as the most significantly regulated pathway in neuro-spheres, although individual nodes of this pathway were distinctly regulated in the two cellular systems. Neurosphere conditions, as opposed to monolayer conditions, cause a transcriptomic and metabolic rewiring that may be crucial for the regulation of stem-like features, where arginine bio-synthesis may be a key metabolic pathway. Additionally, TCGA data from GBM patients showed significant regulation of specific components of the arginine biosynthesis pathway, providing further evidence for the importance of this metabolic pathway in GBM. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 2021-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/150484 |
url |
https://hdl.handle.net/10216/150484 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2072-6694 10.3390/cancers13061327 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136140475760640 |