INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform
Abstract Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55248-0 |
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| author | Chun Ngo Yau Jacky Tin Shing Hung Robert A. A. Campbell Thomas Chun Yip Wong Bei Huang Ben Tin Yan Wong Nick King Ngai Chow Lichun Zhang Eldric Pui Lam Tsoi Yuqi Tan Joshua Jing Xi Li Yun Kwok Wing Hei Ming Lai |
| author_facet | Chun Ngo Yau Jacky Tin Shing Hung Robert A. A. Campbell Thomas Chun Yip Wong Bei Huang Ben Tin Yan Wong Nick King Ngai Chow Lichun Zhang Eldric Pui Lam Tsoi Yuqi Tan Joshua Jing Xi Li Yun Kwok Wing Hei Ming Lai |
| author_sort | Chun Ngo Yau |
| collection | DOAJ |
| description | Abstract Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume. Diverse antigens, mRNAs, neurotransmitters, and post-translational modifications are well-preserved and simultaneously visualized. INSIHGT also allows multi-round, highly multiplexed 3D molecular probing and is compatible with downstream traditional histology and nucleic acid sequencing. With INSIHGT, we map undescribed podocyte-to-parietal epithelial cell microfilaments in mouse glomeruli and neurofilament-intensive inclusion bodies in the human cerebellum, and identify NPY-proximal cell types defined by spatial morpho-proteomics in mouse hypothalamus. We anticipate that INSIHGT can form the foundations for 3D spatial multi-omics technology development and holistic systems biology studies. |
| format | Article |
| id | doaj-art-123b831e831741198d7110301bb0435a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-123b831e831741198d7110301bb0435a2025-01-05T12:35:24ZengNature PortfolioNature Communications2041-17232024-12-0115112010.1038/s41467-024-55248-0INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platformChun Ngo Yau0Jacky Tin Shing Hung1Robert A. A. Campbell2Thomas Chun Yip Wong3Bei Huang4Ben Tin Yan Wong5Nick King Ngai Chow6Lichun Zhang7Eldric Pui Lam Tsoi8Yuqi Tan9Joshua Jing Xi Li10Yun Kwok Wing11Hei Ming Lai12Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongSainsbury Wellcome Centre for Neural Circuits and Behaviour, University College LondonDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Microbiology and Immunology, Stanford UniversityDepartment of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary HospitalDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongDepartment of Psychiatry, Faculty of Medicine, The Chinese University of Hong KongAbstract Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume. Diverse antigens, mRNAs, neurotransmitters, and post-translational modifications are well-preserved and simultaneously visualized. INSIHGT also allows multi-round, highly multiplexed 3D molecular probing and is compatible with downstream traditional histology and nucleic acid sequencing. With INSIHGT, we map undescribed podocyte-to-parietal epithelial cell microfilaments in mouse glomeruli and neurofilament-intensive inclusion bodies in the human cerebellum, and identify NPY-proximal cell types defined by spatial morpho-proteomics in mouse hypothalamus. We anticipate that INSIHGT can form the foundations for 3D spatial multi-omics technology development and holistic systems biology studies.https://doi.org/10.1038/s41467-024-55248-0 |
| spellingShingle | Chun Ngo Yau Jacky Tin Shing Hung Robert A. A. Campbell Thomas Chun Yip Wong Bei Huang Ben Tin Yan Wong Nick King Ngai Chow Lichun Zhang Eldric Pui Lam Tsoi Yuqi Tan Joshua Jing Xi Li Yun Kwok Wing Hei Ming Lai INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform Nature Communications |
| title | INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform |
| title_full | INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform |
| title_fullStr | INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform |
| title_full_unstemmed | INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform |
| title_short | INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform |
| title_sort | insihgt an accessible multi scale multi modal 3d spatial biology platform |
| url | https://doi.org/10.1038/s41467-024-55248-0 |
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