Cellular and Molecular Probing of Intact Human Organs
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Optical tissue transparency permits scalable cellular and molecular investigation of complex tissues in 3D. Adult human organs are particularly challenging to render transparent because of the accumulation of dense and sturdy molecules in decades-aged tissues. To overcome these challenges, we developed SHANEL, a method based on a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to render the intact adult human brain and kidney transparent and perform 3D histology with antibodies and dyes in centimeters-depth. Thereby, we revealed structural details of the intact human eye, human thyroid, human kidney, and transgenic pig pancreas at the cellular resolution. Furthermore, we developed a deep learning pipeline to analyze millions of cells in cleared human brain tissues within hours with standard lab computers. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of large intact mammalian organs.
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Advanced tissue-clearing methods combined with fluorescence microscopy have enabled the visualization of large samples, including entire mouse bodies and big human tissue specimens at the single-cell resolution.
“Advanced tissue-clearing methods combined with fluorescence microscopy have enabled the visualization of large samples, including entire mouse bodies and big human tissue specimens at the single-cell resolution1–5.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [3]
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- Authors
- Zhao, S., Todorov, M. I., Cai, R., -Maskari, R. A., Steinke, H., Kemter, E., Mai, H., Rong, Z., Warmer, M., Stanic, K., Schoppe, O., Paetzold, J. C., Gesierich, B., Wong, M. N., Huber, T. B., Duering, M., Bruns, O. T., Menze, B., Lipfert, J., Puelles, V. G., Wolf, E., Bechmann, I., & Ertürk, A.
- Affiliations
- Helmholtz Munich (DE)
- Leipzig University (DE)
- German Center for Diabetes Research (DE)
- Technical University of Munich (DE)
- Institut für Schlaganfall- und Demenzforschung (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- LMU Klinikum (DE)
- Center for NanoScience (DE)
- Corresponding author
- Ertürk, Ali
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 180
- Issue
- 4
- Pages
- 796-812.e19
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7557154
- OpenAlex
- W3005867992
- Cited by
- 292
- References
- 114
- Citations by year
- 2026: 36 · 2025: 43 · 2024: 43 · 2023: 35 · 2022: 49 · 2021: 60 · 2020: 26
- FWCI
- 20.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Site cant be reached (submittedVersion, other-oa)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- Fritz Thyssen Stiftung
- Deutsche Forschungsgemeinschaft (ER 810/2-1, SFB 1052, TRR127, CRC/1192, BR 5355/2-1, 390857198)
- Bundesministerium für Bildung und Forschung (INST 409/193-1 FUGG)
- European Commission (01EW1501A)
- Stiftung zur Erforschung der Vaskulären Demenz
- National Health and Medical Research Council
- Alexander von Humboldt-Stiftung
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Keywords
- tissue clearing, human brain, human kidney, human eye, human thyroid, 3D histology, antibody labeling
- MeSH terms
- Deep Learning, Aged, 80 and over, Animals, Brain, Eye, Female, Humans, Kidney, Male, Middle Aged, Pancreas, Staining and Labeling, Swine, Thyroid Gland, Imaging, Three-Dimensional, Mice, Limit of Detection, Optical Imaging
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