Bio-MAX Institute, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Electrical and Computer Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Nat Commun. 2022 May 9;13(1):2540. doi: 10.1038/s41467-022-30299-3.
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.
转录后修饰特征，如单碱基 RNA 编辑，是癌症中转录多样性的来源，但在肿瘤微环境中的空间背景方面知之甚少。在这里，我们引入了空间组织病理学检查与测序相结合的转录后修饰组学（Select-seq），该方法可以从免疫荧光染色的组织中分离出感兴趣的区域，并获得转录组和转录后修饰组数据。通过 Select-seq，我们分析了与三阴性乳腺癌患者肿瘤微环境相关的癌症干细胞样微环境。我们鉴定了可变剪接变体，对浸润 T 细胞和 B 细胞进行了互补决定区分析，并评估了肿瘤组织切片中的腺嘌呤到肌苷的碱基编辑。特别是在三阴性乳腺癌微环境中，鉴定了不同微环境组特异性的腺嘌呤到肌苷的编辑组。
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