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

• DOI: 10.1038/s41467-022-30299-3
• Publication Date: 2022-05-09T10:03:05Z
• Authors: Amos C. Lee; Yongju Lee; Ahyoun Choi; Han-Byoel Lee; Kyoungseob Shin; Hyunho Lee; Ji Young Kim; Han Suk Ryu; Hoe Suk Kim; Seung Yeon Ryu; Sangeun Lee; Jong-Ho Cheun; Duck Kyun Yoo; Sumin Lee; Hansol Choi; Taehoon Ryu; Huiran Yeom; Namphil Kim; Jinsung Noh; Yonghee Lee; Inyoung Kim; Sangwook 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
• Keywords: 0301 basic medicine; Adenosine; Adenosine Deaminase; Science; Q; 0206 medical engineering; Triple Negative Breast Neoplasms; 02 engineering and technology; Article; Inosine; 3. Good health; 03 medical and health sciences; Neoplastic Stem Cells; Tumor Microenvironment; Humans

AbstractEpitranscriptomic 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.