Uniform volumetric single-cell processing for organ-scale molecular phenotyping
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 ad...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2025
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| Online Access: | https://hdl.handle.net/1721.1/158176 |
| _version_ | 1824458354784731136 |
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| author | Yun, Dae Hee Park, Young-Gyun Cho, Jae Hun Kamentsky, Lee Evans, Nicholas B DiNapoli, Nicholas Xie, Katherine Choi, Seo Woo Albanese, Alexandre Tian, Yuxuan Sohn, Chang Ho Zhang, Qiangge Kim, Minyoung E Swaney, Justin Guan, Webster Park, Juhyuk Drummond, Gabi Choi, Heejin Ruelas, Luzdary Feng, Guoping Chung, Kwanghun |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Yun, Dae Hee Park, Young-Gyun Cho, Jae Hun Kamentsky, Lee Evans, Nicholas B DiNapoli, Nicholas Xie, Katherine Choi, Seo Woo Albanese, Alexandre Tian, Yuxuan Sohn, Chang Ho Zhang, Qiangge Kim, Minyoung E Swaney, Justin Guan, Webster Park, Juhyuk Drummond, Gabi Choi, Heejin Ruelas, Luzdary Feng, Guoping Chung, Kwanghun |
| author_sort | Yun, Dae Hee |
| collection | MIT |
| description | 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. |
| first_indexed | 2025-02-19T04:24:34Z |
| format | Article |
| id | mit-1721.1/158176 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:24:34Z |
| publishDate | 2025 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1581762025-02-05T19:45:00Z Uniform volumetric single-cell processing for organ-scale molecular phenotyping Yun, Dae Hee Park, Young-Gyun Cho, Jae Hun Kamentsky, Lee Evans, Nicholas B DiNapoli, Nicholas Xie, Katherine Choi, Seo Woo Albanese, Alexandre Tian, Yuxuan Sohn, Chang Ho Zhang, Qiangge Kim, Minyoung E Swaney, Justin Guan, Webster Park, Juhyuk Drummond, Gabi Choi, Heejin Ruelas, Luzdary Feng, Guoping Chung, Kwanghun Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemical Engineering McGovern Institute for Brain Research at MIT Broad Institute of MIT and Harvard 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. 2025-02-05T19:44:58Z 2025-02-05T19:44:58Z 2025-01-24 2025-02-05T19:28:06Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/158176 Yun, D.H., Park, YG., Cho, J.H. et al. Uniform volumetric single-cell processing for organ-scale molecular phenotyping. Nat Biotechnol (2025). en 10.1038/s41587-024-02533-4 Nature Biotechnology Creative Commons Attribution-Noncommercial-ShareAlike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf application/zip Springer Science and Business Media LLC Author |
| spellingShingle | Yun, Dae Hee Park, Young-Gyun Cho, Jae Hun Kamentsky, Lee Evans, Nicholas B DiNapoli, Nicholas Xie, Katherine Choi, Seo Woo Albanese, Alexandre Tian, Yuxuan Sohn, Chang Ho Zhang, Qiangge Kim, Minyoung E Swaney, Justin Guan, Webster Park, Juhyuk Drummond, Gabi Choi, Heejin Ruelas, Luzdary Feng, Guoping Chung, Kwanghun Uniform volumetric single-cell processing for organ-scale molecular phenotyping |
| title | Uniform volumetric single-cell processing for organ-scale molecular phenotyping |
| title_full | Uniform volumetric single-cell processing for organ-scale molecular phenotyping |
| title_fullStr | Uniform volumetric single-cell processing for organ-scale molecular phenotyping |
| title_full_unstemmed | Uniform volumetric single-cell processing for organ-scale molecular phenotyping |
| title_short | Uniform volumetric single-cell processing for organ-scale molecular phenotyping |
| title_sort | uniform volumetric single cell processing for organ scale molecular phenotyping |
| url | https://hdl.handle.net/1721.1/158176 |
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