Whole-brain spatial transcriptional analysis at cellular resolution
Recent advances in RNA analysis have deepened our understanding of cellular states in biological tissues. However, a substantial gap remains in integrating RNA expression data with spatial context across organs, primarily owing to the challenges associated with RNA detection within intact tissue vol...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2024-11, Vol.386 (6724), p.907-915 |
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| creator | Kanatani, Shigeaki Kreutzmann, Judith C Li, Yue West, Zoe Larsen, Lea Lydolph Nikou, Danai Vougesi Eidhof, Ilse Walton, Abigail Zhang, Songbai Rodríguez-Kirby, Leslie Rubio Skytte, Jacob Lercke Salinas, Casper Gravesen Takamatsu, Kimiharu Li, Xiaofei Tanaka, Daisuke H Kaczynska, Dagmara Fukumoto, Keishiro Karamzadeh, Razieh Xiang, Yujiao Uesaka, Naofumi Tanabe, Tsutomu Adner, Mikael Hartman, Johan Miyakawa, Ayako Sundström, Erik Castelo-Branco, Gonçalo Roostalu, Urmas Hecksher-Sørensen, Jacob Uhlén, Per |
| description | Recent advances in RNA analysis have deepened our understanding of cellular states in biological tissues. However, a substantial gap remains in integrating RNA expression data with spatial context across organs, primarily owing to the challenges associated with RNA detection within intact tissue volumes. Here, we developed Tris buffer-mediated retention of in situ hybridization chain reaction signal in cleared organs (TRISCO), an effective tissue-clearing method designed for whole-brain spatial three-dimensional (3D) RNA imaging. TRISCO resolved several crucial issues, including the preservation of RNA integrity, achieving uniform RNA labeling, and enhancing tissue transparency. We tested TRISCO using a broad range of cell-identity markers, noncoding and activity-dependent RNAs, within diverse organs of varying sizes and species. TRISCO thus emerges as a powerful tool for single-cell, whole-brain, 3D imaging that enables comprehensive transcriptional spatial analysis across the entire brain. |
| doi_str_mv | 10.1126/science.adn9947 |
| format | Article |
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However, a substantial gap remains in integrating RNA expression data with spatial context across organs, primarily owing to the challenges associated with RNA detection within intact tissue volumes. Here, we developed Tris buffer-mediated retention of in situ hybridization chain reaction signal in cleared organs (TRISCO), an effective tissue-clearing method designed for whole-brain spatial three-dimensional (3D) RNA imaging. TRISCO resolved several crucial issues, including the preservation of RNA integrity, achieving uniform RNA labeling, and enhancing tissue transparency. We tested TRISCO using a broad range of cell-identity markers, noncoding and activity-dependent RNAs, within diverse organs of varying sizes and species. 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Science)</jtitle><addtitle>Science</addtitle><date>2024-11-22</date><risdate>2024</risdate><volume>386</volume><issue>6724</issue><spage>907</spage><epage>915</epage><pages>907-915</pages><issn>0036-8075</issn><issn>1095-9203</issn><eissn>1095-9203</eissn><abstract>Recent advances in RNA analysis have deepened our understanding of cellular states in biological tissues. However, a substantial gap remains in integrating RNA expression data with spatial context across organs, primarily owing to the challenges associated with RNA detection within intact tissue volumes. Here, we developed Tris buffer-mediated retention of in situ hybridization chain reaction signal in cleared organs (TRISCO), an effective tissue-clearing method designed for whole-brain spatial three-dimensional (3D) RNA imaging. TRISCO resolved several crucial issues, including the preservation of RNA integrity, achieving uniform RNA labeling, and enhancing tissue transparency. We tested TRISCO using a broad range of cell-identity markers, noncoding and activity-dependent RNAs, within diverse organs of varying sizes and species. TRISCO thus emerges as a powerful tool for single-cell, whole-brain, 3D imaging that enables comprehensive transcriptional spatial analysis across the entire brain.</abstract><cop>United States</cop><pub>The American Association for the Advancement of Science</pub><pmid>39571016</pmid><doi>10.1126/science.adn9947</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3325-6606</orcidid><orcidid>https://orcid.org/0009-0007-1397-1585</orcidid><orcidid>https://orcid.org/0000-0003-1446-1062</orcidid><orcidid>https://orcid.org/0000-0003-0180-3449</orcidid><orcidid>https://orcid.org/0009-0009-1893-7962</orcidid><orcidid>https://orcid.org/0000-0003-0584-1119</orcidid><orcidid>https://orcid.org/0000-0003-2247-9393</orcidid><orcidid>https://orcid.org/0000-0003-0313-2124</orcidid><orcidid>https://orcid.org/0000-0002-1435-709X</orcidid><orcidid>https://orcid.org/0009-0008-1915-5658</orcidid><orcidid>https://orcid.org/0000-0003-3485-8331</orcidid><orcidid>https://orcid.org/0000-0003-3000-9105</orcidid><orcidid>https://orcid.org/0000-0002-9744-944X</orcidid><orcidid>https://orcid.org/0009-0003-3781-4972</orcidid><orcidid>https://orcid.org/0000-0002-5941-4000</orcidid><orcidid>https://orcid.org/0000-0003-1634-4759</orcidid><orcidid>https://orcid.org/0000-0002-7849-2055</orcidid><orcidid>https://orcid.org/0000-0003-2931-8015</orcidid><orcidid>https://orcid.org/0000-0002-1567-3078</orcidid><orcidid>https://orcid.org/0000-0002-6500-8527</orcidid><orcidid>https://orcid.org/0000-0002-9991-7534</orcidid><orcidid>https://orcid.org/0000-0002-5516-6177</orcidid><orcidid>https://orcid.org/0000-0003-2226-4288</orcidid><orcidid>https://orcid.org/0000-0003-4467-2661</orcidid><orcidid>https://orcid.org/0000-0002-1238-6444</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2024-11, Vol.386 (6724), p.907-915 |
| issn | 0036-8075 1095-9203 1095-9203 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_893156 |
| source | MEDLINE; American Association for the Advancement of Science |
| subjects | Animals Brain Brain - metabolism Gene expression Gene Expression Profiling - methods Hybridization Imaging, Three-Dimensional Immediate-early proteins In Situ Hybridization Localization Mice Molecular Imaging - methods RNA - genetics RNA - metabolism Single-Cell Analysis - methods Spatial analysis Three dimensional analysis Transcription, Genetic Transcriptomics |
| title | Whole-brain spatial transcriptional analysis at cellular resolution |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T23%3A09%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Whole-brain%20spatial%20transcriptional%20analysis%20at%20cellular%20resolution&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Kanatani,%20Shigeaki&rft.date=2024-11-22&rft.volume=386&rft.issue=6724&rft.spage=907&rft.epage=915&rft.pages=907-915&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.adn9947&rft_dat=%3Cproquest_swepu%3E3131467071%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3131467071&rft_id=info:pmid/39571016&rfr_iscdi=true |