Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function

Detalhes bibliográficos
Autor(a) principal: Sobral, Daniel
Data de Publicação: 2022
Outros Autores: Francisco, Rita, Duro, Laura, Videira, Paula Alexandra, Grosso, Ana Rita
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/145886
Resumo: Funding Information: This work was financed by national funds from Fundação para a Ciência e Tecnologia (FCT), in the scope of the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.This work had also the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Publisher Copyright: © 2022 by the authors.
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spelling Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Functioncancergenomicsglycosylation machineryhealthy tissuestranscriptomicsMedicine (miscellaneous)Biochemistry, Genetics and Molecular Biology(all)SDG 3 - Good Health and Well-beingFunding Information: This work was financed by national funds from Fundação para a Ciência e Tecnologia (FCT), in the scope of the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.This work had also the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Publisher Copyright: © 2022 by the authors.Glycosylation is a fundamental cellular process affecting human development and health. Complex machinery establishes the glycan structures whose heterogeneity provides greater structural diversity than other post-translational modifications. Although known to present spatial and temporal diversity, the evolution of glycosylation and its role at the tissue-specific level is poorly understood. In this study, we combined genome and transcriptome profiles of healthy and diseased tissues to uncover novel insights into the complex role of glycosylation in humans. We constructed a catalogue of human glycosylation factors, including transferases, hydrolases and other genes directly involved in glycosylation. These were categorized as involved in N-, O- and lipid-linked glycosylation, glypiation, and glycosaminoglycan synthesis. Our data showed that these glycosylation factors constitute an ancient family of genes, where evolutionary constraints suppressed large gene duplications, except for genes involved in O-linked and lipid glycosylation. The transcriptome profiles of 30 healthy human tissues revealed tissue-specific expression patterns preserved across mammals. In addition, clusters of tightly co-expressed genes suggest a glycosylation code underlying tissue identity. Interestingly, several glycosylation factors showed tissue-specific profiles varying with age, suggesting a role in ageing-related disorders. In cancer, our analysis revealed that glycosylation factors are highly perturbed, at the genome and transcriptome levels, with a strong predominance of copy number alterations. Moreover, glycosylation factor dysregulation was associated with distinct cellular compositions of the tumor microenvironment, reinforcing the impact of glycosylation in modulating the immune system. Overall, this work provides genome-wide evidence that the glycosylation machinery is tightly regulated in healthy tissues and impaired in ageing and tumorigenesis, unveiling novel potential roles as prognostic biomarkers or therapeutic targets.UCIBIO - Applied Molecular Biosciences UnitDCV - Departamento de Ciências da VidaRUNSobral, DanielFrancisco, RitaDuro, LauraVideira, Paula AlexandraGrosso, Ana Rita2022-11-29T22:11:34Z2022-082022-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article21application/pdfhttp://hdl.handle.net/10362/145886eng2227-9059PURE: 46653624https://doi.org/10.3390/biomedicines10081805info: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:RCAAP2024-05-22T18:07:02Zoai:run.unl.pt:10362/145886Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:07:02Repositório 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 Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
title Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
spellingShingle Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
Sobral, Daniel
cancer
genomics
glycosylation machinery
healthy tissues
transcriptomics
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
title_short Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
title_full Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
title_fullStr Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
title_full_unstemmed Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
title_sort Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
author Sobral, Daniel
author_facet Sobral, Daniel
Francisco, Rita
Duro, Laura
Videira, Paula Alexandra
Grosso, Ana Rita
author_role author
author2 Francisco, Rita
Duro, Laura
Videira, Paula Alexandra
Grosso, Ana Rita
author2_role author
author
author
author
dc.contributor.none.fl_str_mv UCIBIO - Applied Molecular Biosciences Unit
DCV - Departamento de Ciências da Vida
RUN
dc.contributor.author.fl_str_mv Sobral, Daniel
Francisco, Rita
Duro, Laura
Videira, Paula Alexandra
Grosso, Ana Rita
dc.subject.por.fl_str_mv cancer
genomics
glycosylation machinery
healthy tissues
transcriptomics
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
topic cancer
genomics
glycosylation machinery
healthy tissues
transcriptomics
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
SDG 3 - Good Health and Well-being
description Funding Information: This work was financed by national funds from Fundação para a Ciência e Tecnologia (FCT), in the scope of the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.This work had also the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Publisher Copyright: © 2022 by the authors.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-29T22:11:34Z
2022-08
2022-08-01T00:00:00Z
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 http://hdl.handle.net/10362/145886
url http://hdl.handle.net/10362/145886
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2227-9059
PURE: 46653624
https://doi.org/10.3390/biomedicines10081805
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 21
application/pdf
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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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