Whole-brain spatial transcriptional analysis at cellular resolution

• 成果类型: Article
• 署名作者: Kanatani, Shigeaki; Kreutzmann, Judith C.; Li, Yue; West, Zoe; Larsen, Lea Lydolph; Nikou, Danai Vougesi; Eidhof, Ilse; Walton, Abigail; Zhang, Songbai; Rodriguez-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; Sundstrom, Erik; Castelo-Branco, Goncalo; Roostalu, Urmas; Hecksher-Sorensen, Jacob; Uhlen, Per
• 署名单位: Karolinska Institutet; Keio University; Karolinska Institutet; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Institute of Science Tokyo; Karolinska Institutet; Karolinska Institutet; Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet; Karolinska University Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8126
• DOI: 10.1126/science.adn9947
• 发表日期: 2024-11-22
• 页码: 907-915
• 关键词: tissue; cost; rna

摘要

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.