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

Abstract

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.

Type Journal
ISBN 1546-1718 (Electronic) 1061-4036 (Linking)
Authors Wu, S. Z.; Al-Eryani, G.; Roden, D. L.; Junankar, S.; Harvey, K.; Andersson, A.; Thennavan, A.; Wang, C.; Torpy, J. R.; Bartonicek, N.; Wang, T.; Larsson, L.; Kaczorowski, D.; Weisenfeld, N. I.; Uytingco, C. R.; Chew, J. G.; Bent, Z. W.; Chan, C. L.; Gnanasambandapillai, V.; Dutertre, C. A.; Gluch, L.; Hui, M. N.; Beith, J.; Parker, A.; Robbins, E.; Segara, D.; Cooper, C.; Mak, C.; Chan, B.; Warrier, S.; Ginhoux, F.; Millar, E.; Powell, J. E.; Williams, S. R.; Liu, X. S.; O'Toole, S.; Lim, E.; Lundeberg, J.; Perou, C. M.; Swarbrick, A.
Responsible Garvan Author A/Prof Alex Swarbrick
Publisher Name NATURE GENETICS
Published Date 2021-09-30
Published Volume 53
Published Issue 9
Published Pages 1334-1347
Status Published in-print
DOI 10.1038/s41588-021-00911-1
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/34493872