Journal Article

A single-cell and spatially resolved atlas of human breast cancers

Gnanasambandapillai, Vikkitharan, Robbins, Elizabeth, Liu, X. Shirley, Mak, Cindy, Lim, Elgene, Bartonicek, Nenad, Parker, Andrew, Wu, Sunny Z., Millar, Ewan, Chan, Belinda, Wang, Taopeng, Powell, Joseph E., Roden, Daniel Lee, Chew, Jennifer G., Williams, Stephen R., Beith, Jane, Hui, Mun N., Larsson, Ludvig, Torpy, James R., Chan, Chia-Ling, Ginhoux, Florent, Cooper, Caroline, Junankar, Simon, Andersson, Alma, Al-Eryani, Ghamdan, Dutertre, Charles-Antoine, Weisenfeld, Neil I., Thennavan, Aatish, Wang, Chenfei, O’Toole, Sandra, Harvey, Kate, Bent, Zachary W., Swarbrick, Alexander, Gluch, Laurence, Kaczorowski, Dominik, Uytingco, Cedric R., Warrier, Sanjay, Segara, Davendra, Perou, Charles M., Lundeberg, Joakim

2021

Overview

Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2 + macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer. A multi-omic atlas of breast cancers, integrating single-cell RNA sequencing, spatial transcriptomics and immunophenotyping, identifies nine ecotypes associated with cellular heterogeneity and prognosis.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/67/1347 / 631/67/327 / Agriculture / Animal Genetics and Genomics / B-Lymphocytes - immunology / B7-H1 Antigen - genetics / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - immunology / Breast Neoplasms - pathology / Cancer Research / Cancer therapies / Care and treatment / CD8-Positive T-Lymphocytes - immunology / Cell differentiation / Cell surface / Composition / Datasets / Development and progression / Ecotypes / Endothelial Cells - metabolism / Epitopes / Female / Gene expression / Gene Expression Regulation, Neoplastic - genetics / Gene Function / Genetic aspects / Genetic transcription / Health aspects / Heterogeneity / Histology / Human Genetics / Humans / Immunoregulation / Macrophages / Macrophages - cytology / Macrophages - immunology / Membrane Proteins - genetics / Mesenchyme / Myeloid Cells - immunology / Myeloid Cells - metabolism / PD-L1 protein / Prognosis / RNA sequencing / Sequence Analysis, RNA / Single-Cell Analysis / Taxonomy / Transcription / Transcriptome - genetics / Transcriptomes / Tumor Microenvironment / Tumor Suppressor Proteins - genetics / Tumors