Integrated platform for multi-scale molecular imaging and phenotyping of the human brain

• 成果类型: Article
• 署名作者: Park, Juhyuk; Wang, Ji; Guan, Webster; Gjesteby, Lars A.; Pollack, Dylan; Kamentsky, Lee; Evans, Nicholas B.; Stirman, Jeff; Gu, Xinyi; Zhao, Chuanxi; Marx, Slayton; Kim, Minyoung E.; Choi, Seo Woo; Snyder, Michael; Chavez, David; Su-Arcaro, Clover; Tian, Yuxuan; Park, Chang Sin; Zhang, Qiangge; Yun, Dae Hee; Moukheiber, Mira; Feng, Guoping; Yang, X. William; Keene, C. Dirk; Hof, Patrick R.; Ghosh, Satrajit S.; Frosch, Matthew P.; Brattain, Laura J.; Chung, Kwanghun
• 署名单位: Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Institute for Basic Science - Korea (IBS); Lincoln Laboratory; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; Massachusetts Institute of Technology (MIT); University of Washington; University of Washington Seattle; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Seoul National University (SNU)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10190
• DOI: 10.1126/science.adh9979
• 发表日期: 2024-06-14
• 关键词: stereologic analysis; alzheimers-disease; cerebral-cortex; amyloid-beta; tissue; reconstruction; neurons; atlas; tau

摘要

Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel-based tissue processing technology for multiplexed multiscale imaging of human organ-scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer's disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.