Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles

Abstract This study presents “mouse tissue glycome atlas” representing the profiles of major N-glycans of mouse glycoproteins that may define their essential functions in the surface glycocalyx of mouse organs/tissues and serum-derived extracellular vesicles (exosomes). Cell surface glycocalyx compo...

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Main Authors: Michiru Otaki, Nozomi Hirane, Yayoi Natsume-Kitatani, Mari Nogami Itoh, Masanori Shindo, Yoichi Kurebayashi, Shin-Ichiro Nishimura
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-21758-4
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author Michiru Otaki
Nozomi Hirane
Yayoi Natsume-Kitatani
Mari Nogami Itoh
Masanori Shindo
Yoichi Kurebayashi
Shin-Ichiro Nishimura
author_facet Michiru Otaki
Nozomi Hirane
Yayoi Natsume-Kitatani
Mari Nogami Itoh
Masanori Shindo
Yoichi Kurebayashi
Shin-Ichiro Nishimura
author_sort Michiru Otaki
collection DOAJ
description Abstract This study presents “mouse tissue glycome atlas” representing the profiles of major N-glycans of mouse glycoproteins that may define their essential functions in the surface glycocalyx of mouse organs/tissues and serum-derived extracellular vesicles (exosomes). Cell surface glycocalyx composed of a variety of N-glycans attached covalently to the membrane proteins, notably characteristic “N-glycosylation patterns” of the glycocalyx, plays a critical role for the regulation of cell differentiation, cell adhesion, homeostatic immune response, and biodistribution of secreted exosomes. Given that the integrity of cell surface glycocalyx correlates significantly with maintenance of the cellular morphology and homeostatic immune functions, dynamic alterations of N-glycosylation patterns in the normal glycocalyx caused by cellular abnormalities may serve as highly sensitive and promising biomarkers. Although it is believed that inter-organs variations in N-glycosylation patterns exist, information of the glycan diversity in mouse organs/tissues remains to be elusive. Here we communicate for the first-time N-glycosylation patterns of 16 mouse organs/tissues, serum, and serum-derived exosomes of Slc:ddY mice using an established solid-phase glycoblotting platform for the rapid, easy, and high throughput MALDI-TOFMS-based quantitative glycomics. The present results elicited occurrence of the organ/tissue-characteristic N-glycosylation patterns that can be discriminated to each other. Basic machine learning analysis using this N-glycome dataset enabled classification between 16 mouse organs/tissues with the highest F1 score (69.7–100%) when neural network algorithm was used. A preliminary examination demonstrated that machine learning analysis of mouse lung N-glycome dataset by random forest algorithm allows for the discrimination of lungs among the different mouse strains such as the outbred mouse Slc:ddY, inbred mouse DBA/2Crslc, and systemic lupus erythematosus model mouse MRL-lpr/lpr with the highest F1 score (74.5–83.8%). Our results strongly implicate importance of “human organ/tissue glycome atlas” for understanding the crucial and diversified roles of glycocalyx determined by the organ/tissue-characteristic N-glycosylation patterns and the discovery research for N-glycome-based disease-specific biomarkers and therapeutic targets.
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spelling doaj.art-5de9196a41814d5181581bf61c0511852022-12-22T03:53:47ZengNature PortfolioScientific Reports2045-23222022-10-0112111510.1038/s41598-022-21758-4Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profilesMichiru Otaki0Nozomi Hirane1Yayoi Natsume-Kitatani2Mari Nogami Itoh3Masanori Shindo4Yoichi Kurebayashi5Shin-Ichiro Nishimura6Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido UniversityField of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido UniversityLaboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and NutritionLaboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and NutritionLaboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and NutritionField of Artificial Intelligence and Digital Health Science, Graduate School of Medicine, Kobe UniversityField of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido UniversityAbstract This study presents “mouse tissue glycome atlas” representing the profiles of major N-glycans of mouse glycoproteins that may define their essential functions in the surface glycocalyx of mouse organs/tissues and serum-derived extracellular vesicles (exosomes). Cell surface glycocalyx composed of a variety of N-glycans attached covalently to the membrane proteins, notably characteristic “N-glycosylation patterns” of the glycocalyx, plays a critical role for the regulation of cell differentiation, cell adhesion, homeostatic immune response, and biodistribution of secreted exosomes. Given that the integrity of cell surface glycocalyx correlates significantly with maintenance of the cellular morphology and homeostatic immune functions, dynamic alterations of N-glycosylation patterns in the normal glycocalyx caused by cellular abnormalities may serve as highly sensitive and promising biomarkers. Although it is believed that inter-organs variations in N-glycosylation patterns exist, information of the glycan diversity in mouse organs/tissues remains to be elusive. Here we communicate for the first-time N-glycosylation patterns of 16 mouse organs/tissues, serum, and serum-derived exosomes of Slc:ddY mice using an established solid-phase glycoblotting platform for the rapid, easy, and high throughput MALDI-TOFMS-based quantitative glycomics. The present results elicited occurrence of the organ/tissue-characteristic N-glycosylation patterns that can be discriminated to each other. Basic machine learning analysis using this N-glycome dataset enabled classification between 16 mouse organs/tissues with the highest F1 score (69.7–100%) when neural network algorithm was used. A preliminary examination demonstrated that machine learning analysis of mouse lung N-glycome dataset by random forest algorithm allows for the discrimination of lungs among the different mouse strains such as the outbred mouse Slc:ddY, inbred mouse DBA/2Crslc, and systemic lupus erythematosus model mouse MRL-lpr/lpr with the highest F1 score (74.5–83.8%). Our results strongly implicate importance of “human organ/tissue glycome atlas” for understanding the crucial and diversified roles of glycocalyx determined by the organ/tissue-characteristic N-glycosylation patterns and the discovery research for N-glycome-based disease-specific biomarkers and therapeutic targets.https://doi.org/10.1038/s41598-022-21758-4
spellingShingle Michiru Otaki
Nozomi Hirane
Yayoi Natsume-Kitatani
Mari Nogami Itoh
Masanori Shindo
Yoichi Kurebayashi
Shin-Ichiro Nishimura
Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles
Scientific Reports
title Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles
title_full Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles
title_fullStr Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles
title_full_unstemmed Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles
title_short Mouse tissue glycome atlas 2022 highlights inter-organ variation in major N-glycan profiles
title_sort mouse tissue glycome atlas 2022 highlights inter organ variation in major n glycan profiles
url https://doi.org/10.1038/s41598-022-21758-4
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