Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification

Abstract Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity‐anchored in situ spectral coding amplification...

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Main Authors: Xiaolei Chen, Ruijie Deng, Dongdong Su, Xiaochen Ma, Xu Han, Shizheng Wang, Yuqing Xia, Zifu Yang, Ningqiang Gong, Yanwei Jia, Xueyun Gao, Xiaojun Ren
Format: Article
Language:English
Published: Wiley 2023-10-01
Series:Exploration
Subjects:
Online Access:https://doi.org/10.1002/EXP.20220175
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author Xiaolei Chen
Ruijie Deng
Dongdong Su
Xiaochen Ma
Xu Han
Shizheng Wang
Yuqing Xia
Zifu Yang
Ningqiang Gong
Yanwei Jia
Xueyun Gao
Xiaojun Ren
author_facet Xiaolei Chen
Ruijie Deng
Dongdong Su
Xiaochen Ma
Xu Han
Shizheng Wang
Yuqing Xia
Zifu Yang
Ningqiang Gong
Yanwei Jia
Xueyun Gao
Xiaojun Ren
author_sort Xiaolei Chen
collection DOAJ
description Abstract Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity‐anchored in situ spectral coding amplification (ProxISCA) is proposed for multiplexed imaging of RNA mutations, enabling visual typing of brain gliomas with different pathological grades at the single‐cell and tissue levels. The ligation‐based padlock probe can discriminate one‐nucleotide variations, and the design of proximity primers enables the anchoring of amplicons on target RNA, thus improving localization accuracy. The DNA module‐based spectral coding strategy can dramatically improve the multiplexing capacity for imaging RNA mutations through one‐time labelling, with low cost and simple operation. One‐target‐one‐amplicon amplification confers ProxISCA the ability to quantify RNA mutation copy number with single‐molecule resolution. Based on this approach, it is found that gliomas with higher malignant grades express more genes with high correlation at the cellular and tissue levels and show greater cellular heterogeneity. ProxISCA provides a tool for glioma research and precise diagnosis, which can reveal the relationship between cellular heterogeneity and glioma occurrence or development and assist in pathological prognosis.
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spelling doaj.art-5c15e10989c74c2fb1ae92743d2b7d862023-10-18T06:54:41ZengWileyExploration2766-85092766-20982023-10-0135n/an/a10.1002/EXP.20220175Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplificationXiaolei Chen0Ruijie Deng1Dongdong Su2Xiaochen Ma3Xu Han4Shizheng Wang5Yuqing Xia6Zifu Yang7Ningqiang Gong8Yanwei Jia9Xueyun Gao10Xiaojun Ren11Department of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaCollege of Biomass Science and Engineering Healthy Food Evaluation Research Center Sichuan University ChengduChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaInstitute of High Energy Physics Chinese Academy of Sciences BeijingChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaDepartment of Bioengineering University of Pennsylvania PhiladelphiaUSAState‐Key Laboratory of Analog and Mixed‐Signal VLSI Institute of Microelectronics University of Macau MacauChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaDepartment of Chemistry and Biology Faculty of Environment and Life Science Beijing University of Technology BeijingChinaAbstract Gliomas are histologically and genetically heterogeneous tumors. However, classical histopathological typing often ignores the high heterogeneity of tumors and thus cannot meet the requirements of precise pathological diagnosis. Here, proximity‐anchored in situ spectral coding amplification (ProxISCA) is proposed for multiplexed imaging of RNA mutations, enabling visual typing of brain gliomas with different pathological grades at the single‐cell and tissue levels. The ligation‐based padlock probe can discriminate one‐nucleotide variations, and the design of proximity primers enables the anchoring of amplicons on target RNA, thus improving localization accuracy. The DNA module‐based spectral coding strategy can dramatically improve the multiplexing capacity for imaging RNA mutations through one‐time labelling, with low cost and simple operation. One‐target‐one‐amplicon amplification confers ProxISCA the ability to quantify RNA mutation copy number with single‐molecule resolution. Based on this approach, it is found that gliomas with higher malignant grades express more genes with high correlation at the cellular and tissue levels and show greater cellular heterogeneity. ProxISCA provides a tool for glioma research and precise diagnosis, which can reveal the relationship between cellular heterogeneity and glioma occurrence or development and assist in pathological prognosis.https://doi.org/10.1002/EXP.20220175genetic typinggliomain situ imagingmultiplexed detectionRNA mutation
spellingShingle Xiaolei Chen
Ruijie Deng
Dongdong Su
Xiaochen Ma
Xu Han
Shizheng Wang
Yuqing Xia
Zifu Yang
Ningqiang Gong
Yanwei Jia
Xueyun Gao
Xiaojun Ren
Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification
Exploration
genetic typing
glioma
in situ imaging
multiplexed detection
RNA mutation
title Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification
title_full Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification
title_fullStr Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification
title_full_unstemmed Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification
title_short Visual genetic typing of glioma using proximity‐anchored in situ spectral coding amplification
title_sort visual genetic typing of glioma using proximity anchored in situ spectral coding amplification
topic genetic typing
glioma
in situ imaging
multiplexed detection
RNA mutation
url https://doi.org/10.1002/EXP.20220175
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