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Nat. Biotechnol., 24 January 2025 | https://doi.org/10.1038/s41587-024-02533-4
Uniform volumetric single-cell processing for organ-scale molecular phenotyping
Dae Hee Yun 1,2,7, Young-Gyun Park 2,3,7, Jae Hun Cho 4, Lee Kamentsky 2,3, Nicholas B. Evans 2,3, Nicholas DiNapoli 2,3, Katherine Xie 2,3, Seo Woo Choi 2,4, Alexandre Albanese 2,3, Yuxuan Tian 4, Chang Ho Sohn 2,3, Qiangge Zhang 1,5,6, Minyoung E. Kim 1,2, Justin Swaney 4, Webster Guan 4, Juhyuk Park 2,3,4, Gabi Drummond 1, Heejin Choi 2,3, Luzdary Ruelas 4, Guoping Feng 1,5,6 & Kwanghun Chung 1,2,3,4,6
1Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
2Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
3Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
4Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
5Yang Tan Collective and McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
7These authors contributed equally: Dae Hee Yun, Young-Gyun Park.
2Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
3Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
4Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
5Yang Tan Collective and McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
7These authors contributed equally: Dae Hee Yun, Young-Gyun Park.
*Corresponding author: correspondence to Kwanghun Chung
Abstract
Extending single-cell analysis to intact tissues while maintaining organ-scale spatial information poses a major challenge due to unequal chemical processing of densely packed cells. Here we introduce Continuous Redispersion of Volumetric Equilibrium (CuRVE) in nanoporous matrices, a framework to address this challenge. CuRVE ensures uniform processing of all cells in organ-scale tissues by perpetually maintaining dynamic equilibrium of the tissue’s gradually shifting chemical environment. The tissue chemical reaction environment changes at a continuous, slow rate, allowing redispersion of unevenly distributed chemicals and preserving chemical equilibrium tissue wide at any given moment. We implemented CuRVE to immunologically label whole mouse and rat brains and marmoset and human tissue blocks within 1 day. We discovered highly variable regionalized reduction of parvalbumin immunoreactive cells in wild-type adult mice, a phenotype missed by the commonly used genetic labeling. We envision that our platform will advance volumetric single-cell processing and analysis, facilitating comprehensive single-cell level investigations within their spatial context in organ-scale tissues.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-02-11)
- 국외 연구진
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