Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function
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,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/1805 |
| _version_ | 1827618150473007104 |
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| author | Daniel Sobral Rita Francisco Laura Duro Paula Alexandra Videira Ana Rita Grosso |
| author_facet | Daniel Sobral Rita Francisco Laura Duro Paula Alexandra Videira Ana Rita Grosso |
| author_sort | Daniel Sobral |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:00:33Z |
| format | Article |
| id | doaj.art-8a3981ba22aa44fc86e8ebf82415200a |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:00:33Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8a3981ba22aa44fc86e8ebf82415200a2023-12-01T23:27:00ZengMDPI AGBiomedicines2227-90592022-07-01108180510.3390/biomedicines10081805Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and FunctionDaniel Sobral0Rita Francisco1Laura Duro2Paula Alexandra Videira3Ana Rita Grosso4Associate Laboratory i4HB—Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalAssociate Laboratory i4HB—Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, PortugalGlycosylation 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.https://www.mdpi.com/2227-9059/10/8/1805glycosylation machinerygenomicstranscriptomicshealthy tissuescancer |
| spellingShingle | Daniel Sobral Rita Francisco Laura Duro Paula Alexandra Videira Ana Rita Grosso Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function Biomedicines glycosylation machinery genomics transcriptomics healthy tissues cancer |
| title | 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_short | Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function |
| title_sort | concerted regulation of glycosylation factors sustains tissue identity and function |
| topic | glycosylation machinery genomics transcriptomics healthy tissues cancer |
| url | https://www.mdpi.com/2227-9059/10/8/1805 |
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