Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling

Abstract Understanding metabolism is of great significance to decipher various physiological and pathogenic processes. While great progress has been made to profile gene expression, how to capture organ‐, tissue‐, and cell‐type‐specific metabolic profile (i.e., metabolic tissue atlas) in complex mam...

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Main Authors: Xinwen Liu, Lixue Shi, Lingyan Shi, Mian Wei, Zhilun Zhao, Wei Min
Format: Article
Language:English
Published: Wiley 2022-05-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202105437
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author Xinwen Liu
Lixue Shi
Lingyan Shi
Mian Wei
Zhilun Zhao
Wei Min
author_facet Xinwen Liu
Lixue Shi
Lingyan Shi
Mian Wei
Zhilun Zhao
Wei Min
author_sort Xinwen Liu
collection DOAJ
description Abstract Understanding metabolism is of great significance to decipher various physiological and pathogenic processes. While great progress has been made to profile gene expression, how to capture organ‐, tissue‐, and cell‐type‐specific metabolic profile (i.e., metabolic tissue atlas) in complex mammalian systems is lagging behind, largely owing to the lack of metabolic imaging tools with high resolution and high throughput. Here, the authors applied mid‐infrared imaging coupled with heavy water (D2O) metabolic labeling to a scope of mouse organs and tissues. The premise is that, as D2O participates in the biosynthesis of various macromolecules, the resulting broad C‐D vibrational spectrum should interrogate a wide range of metabolic pathways. Applying multivariate analysis to the C‐D spectrum, the authors successfully identified both inter‐organ and intra‐tissue metabolic signatures of mice. A large‐scale metabolic atlas map between different organs from the same mice is thus generated. Moreover, leveraging the power of unsupervised clustering methods, spatially‐resolved metabolic signatures of brain tissues are discovered, revealing tissue and cell‐type specific metabolic profile in situ. As a demonstration of this technique, the authors captured metabolic changes during brain development and characterized intratumoral metabolic heterogeneity of glioblastoma. Altogether, the integrated platform paves a way to map the metabolic tissue atlas for complex mammalian systems.
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spelling doaj.art-b245d80de26649bbb6bf39b5a29bd4792022-12-22T00:29:50ZengWileyAdvanced Science2198-38442022-05-01915n/an/a10.1002/advs.202105437Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water LabelingXinwen Liu0Lixue Shi1Lingyan Shi2Mian Wei3Zhilun Zhao4Wei Min5Department of Chemistry Columbia University New York NY 10027 USADepartment of Chemistry Columbia University New York NY 10027 USADepartment of Chemistry Columbia University New York NY 10027 USADepartment of Chemistry Columbia University New York NY 10027 USADepartment of Chemistry Columbia University New York NY 10027 USADepartment of Chemistry Columbia University New York NY 10027 USAAbstract Understanding metabolism is of great significance to decipher various physiological and pathogenic processes. While great progress has been made to profile gene expression, how to capture organ‐, tissue‐, and cell‐type‐specific metabolic profile (i.e., metabolic tissue atlas) in complex mammalian systems is lagging behind, largely owing to the lack of metabolic imaging tools with high resolution and high throughput. Here, the authors applied mid‐infrared imaging coupled with heavy water (D2O) metabolic labeling to a scope of mouse organs and tissues. The premise is that, as D2O participates in the biosynthesis of various macromolecules, the resulting broad C‐D vibrational spectrum should interrogate a wide range of metabolic pathways. Applying multivariate analysis to the C‐D spectrum, the authors successfully identified both inter‐organ and intra‐tissue metabolic signatures of mice. A large‐scale metabolic atlas map between different organs from the same mice is thus generated. Moreover, leveraging the power of unsupervised clustering methods, spatially‐resolved metabolic signatures of brain tissues are discovered, revealing tissue and cell‐type specific metabolic profile in situ. As a demonstration of this technique, the authors captured metabolic changes during brain development and characterized intratumoral metabolic heterogeneity of glioblastoma. Altogether, the integrated platform paves a way to map the metabolic tissue atlas for complex mammalian systems.https://doi.org/10.1002/advs.202105437heavy water labelinginfrared imagingmetabolic heterogeneitymetabolismmultivariate analysis
spellingShingle Xinwen Liu
Lixue Shi
Lingyan Shi
Mian Wei
Zhilun Zhao
Wei Min
Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling
Advanced Science
heavy water labeling
infrared imaging
metabolic heterogeneity
metabolism
multivariate analysis
title Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling
title_full Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling
title_fullStr Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling
title_full_unstemmed Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling
title_short Towards Mapping Mouse Metabolic Tissue Atlas by Mid‐Infrared Imaging with Heavy Water Labeling
title_sort towards mapping mouse metabolic tissue atlas by mid infrared imaging with heavy water labeling
topic heavy water labeling
infrared imaging
metabolic heterogeneity
metabolism
multivariate analysis
url https://doi.org/10.1002/advs.202105437
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