Journal Article

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

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

2022

Overview

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. The spatial context of epitranscriptomic features in the tumour microenvironment remains poorly understood. Here, a method for transcriptomic and epitranscriptomic analysis of immunofluorescence-stained tissue, Select-seq, is applied to stem cell-like microniches in triple negative breast cancer.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/39 / 38/91 / 631/337/1645/1944 / 631/61/514/1949 / 631/67/1347 / 631/67/69 / Adenosine / Adenosine - genetics / Adenosine Deaminase - genetics / Alternative splicing / Breast cancer / Complementarity-determining region / Context / Editing / Humanities and Social Sciences / Humans / Immunofluorescence / Inosine - genetics / Lymphocytes / Lymphocytes B / Lymphocytes T / Microenvironments / multidisciplinary / Neoplastic Stem Cells / RNA editing / Science / Science (multidisciplinary) / Stem cells / Transcriptomics / Triple Negative Breast Neoplasms / Tumor microenvironment / Tumor Microenvironment - genetics / Tumors