A single-cell and spatially resolved atlas of human breast cancers
| Autor: | Sanjay Warrier, Chenfei Wang, Davendra Segara, Ewan K.A. Millar, Sandra A O'Toole, Ludvig Larsson, Jane Beith, Alma Andersson, Ghamdan Al-Eryani, Charles M. Perou, Dominik C. Kaczorowski, Cindy Mak, Florent Ginhoux, Chia-Ling Chan, James R. Torpy, Aatish Thennavan, Neil I. Weisenfeld, Belinda Chan, Taopeng Wang, Caroline Cooper, Andrew Parker, Joseph E. Powell, Mun N. Hui, Elizabeth Robbins, Cedric Uytingco, Laurence Gluch, Sunny Z. Wu, Stephen R. Williams, Vikkitharan Gnanasambandapillai, Alexander Swarbrick, Charles-Antoine Dutertre, Nenad Bartonicek, Daniel L. Roden, Elgene Lim, Zachary Bent, X. Shirley Liu, Jennifer Chew, Simon Junankar, Joakim Lundeberg, Kate Harvey |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Breast Neoplasms
Computational biology Biology CD8-Positive T-Lymphocytes B7-H1 Antigen Article Transcriptome Immunophenotyping Breast cancer Single-cell analysis Genetics medicine Biomarkers Tumor Tumor Microenvironment Humans Myeloid Cells Regulation of gene expression Tumor microenvironment B-Lymphocytes Sequence Analysis RNA Macrophages Tumor Suppressor Proteins Cancer Endothelial Cells Membrane Proteins medicine.disease Gene Expression Regulation Neoplastic Neoplastic cell Female Single-Cell Analysis |
| Zdroj: | Nat Genet |
| ISSN: | 1546-1718 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink