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Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-022-30299-3

2041-1723

Amos Chungwon Lee, Yong‐Ju Lee, Ahyoun Choi, Han‐Byoel Lee, Kyoungseob Shin, Hyunho Lee, Ji Young Kim, Han Suk Ryu, Hoe Suk Kim, Seung Yeon Ryu, Sang Eun Lee, Jong-Ho Cheun, Duck Kyun Yoo, Sumin Lee, Hansol Choi, Taehoon Ryu, Huiran Yeom, Namphil Kim, Jinsung Noh, Yonghee Lee, Inyoung Kim, Sang-Wook Bae, Jinhyun Kim, Wooseok Lee, Okju Kim, Yushin Jung, Changhoe Kim, Seo Woo Song, Yeongjae Choi, Junho Chung, Byung‐Gee Kim, Wonshik Han, Sunghoon Kwon,

Cancer-related molecular mechanisms research

Abstract Epitranscriptomic features, such as single-base RNA editing, are sources of transcript diversity in cancer, but little is understood in terms of their spatial context in the tumour microenvironment. Here, we introduce spatial-histopathological examination-linked epitranscriptomics converged to transcriptomics with sequencing (Select-seq), which isolates regions of interest from immunofluorescence-stained tissue and obtains transcriptomic and epitranscriptomic data. With Select-seq, we analyse the cancer stem cell-like microniches in relation to the tumour microenvironment of triple-negative breast cancer patients. We identify alternative splice variants, perform complementarity-determining region analysis of infiltrating T cells and B cells, and assess adenosine-to-inosine base editing in tumour tissue sections. Especially, in triple-negative breast cancer microniches, adenosine-to-inosine editome specific to different microniche groups is identified.