Journal
NATURE BIOMEDICAL ENGINEERING
Volume 4, Issue 9, Pages 875-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41551-020-0576-z
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Funding
- Swedish Research Council [2009-3364, 2013-3189, 2017-00815]
- Swedish Cancer Society [CAN 2016-801, 19 0544 Pj, 19 0545 Us]
- Swedish Childhood Cancer Foundation [PR2018-0123]
- Swedish Brain Foundation [FO2018-0209, FO2018-0281]
- Olle Engkvist foundation
- David and Astrid Hagelen Foundation
- Karolinska Institutet Research Foundation
- Takeda Science Foundation
- Kobayashi Foundation for Cancer Research
- Keio Gijuku Academic Development Funds
- Scandinavia-Japan Sasakawa Foundation
- Wenner-Gren Foundation
- Strategic Research Area in Neuroscience (StratNeuro) by the Swedish government
- Strategic Research Area in Stem Cells and Regenerative Medicine (StratRegen) by the Swedish government
- [KAKENHI 18H04906]
- [18K19482]
- [19H03792]
- Swedish Research Council [2017-00815] Funding Source: Swedish Research Council
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A method for the multimodal volumetric imaging of RNAs and proteins in intact tumour volumes and organoids enables the spatial transcriptional profiling of coding RNAs and non-coding RNAs at single-cell resolution in cancer tissues. Microscopy analysis of tumour samples is commonly performed on fixed, thinly sectioned and protein-labelled tissues. However, these examinations do not reveal the intricate three-dimensional structures of tumours, nor enable the detection of aberrant transcripts. Here, we report a method, which we name DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), for the multimodal volumetric imaging of RNAs and proteins in intact tumour volumes and organoids. We used DIIFCO to spatially profile the expression of diverse coding RNAs and non-coding RNAs at the single-cell resolution in a variety of cancer tissues. Quantitative single-cell analysis revealed spatial niches of cancer stem-like cells, and showed that the niches were present at a higher density in triple-negative breast cancer tissue. The improved molecular phenotyping and histopathological diagnosis of cancers may lead to new insights into the biology of tumours of patients.
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