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

Nat Commun. 2022 May 9;13(1):2540. doi: 10.1038/s41467-022-30299-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics
  • Adenosine Deaminase* / genetics
  • Humans
  • Inosine / genetics
  • Neoplastic Stem Cells
  • Triple Negative Breast Neoplasms*
  • Tumor Microenvironment / genetics

Substances

  • Inosine
  • Adenosine Deaminase
  • Adenosine