A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Three-dimensional single-cell imaging for the analysis of RNA and protein expression in intact tumour biopsies
Tekijät: Tanaka N, Kanatani S, Kaczynska D, Fukumoto K, Louhivuori L, Mizutani T, Kopper O, Kronqvist P, Robertson S, Lindh C, Kis L, Pronk R, Niwa N, Matsumoto K, Oya M, Miyakawa A, Falk A, Hartman J, Sahlgren C, Clevers H, Uhlen P
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2020
Journal: Nature Biomedical Engineering
Tietokannassa oleva lehden nimi: NATURE BIOMEDICAL ENGINEERING
Lehden akronyymi: NAT BIOMED ENG
Vuosikerta: 4
Numero: 9
Aloitussivu: 875
Lopetussivu: 888
Sivujen määrä: 17
ISSN: 2157-846X
eISSN: 2157-846X
DOI: https://doi.org/10.1038/s41551-020-0576-z
Tiivistelmä
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.
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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