A single-cell and spatially resolved atlas of human breast cancers
Sunny Z. Wu, Ghamdan Al-Eryani, Daniel Lee Roden, Simon Junankar, Kate Harvey, Alma Andersson, Aatish Thennavan, Chenfei Wang, James R. Torpy, Nenad Bartonicek, Taopeng Wang, Ludvig Larsson, Dominik Kaczorowski, Neil I. Weisenfeld, Cedric R. Uytingco, Jennifer G. Chew, Zachary W. Bent, Chia-Ling Chan, Vikkitharan Gnanasambandapillai, Charles-Antoine Dutertre, Laurence Gluch, Mun N. Hui, Jane Beith, Andrew Parker, Elizabeth Robbins, Davendra Segara, Caroline Cooper, Cindy Mak, Belinda Chan, Sanjay Warrier, Florent Ginhoux, Ewan Millar, Joseph E. Powell, Stephen R. Williams, X. Shirley Liu, Sandra O’Toole, Elgene Lim, Joakim Lundeberg, Charles M. Perou, Alexander Swarbrick
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.
Datasets
1. A single-cell and spatially-resolved atlas of human breast cancers
Metadata
donor_id
celltype_major
celltype_minor
celltype_subset
subtype
gene_module
calls
normal_cell_call
batch_run
multiplexed
cryo_state
development_stage_ontology_term_id
cancer_type
ER
PR
HER2_IHC
HER2_ISH
Ki67
subtype_by_IHC
treatment_status
treatment_details
assay_ontology_term_id
organism_ontology_term_id
tissue_ontology_term_id
suspension_type
sex_ontology_term_id
self_reported_ethnicity_ontology_term_id
disease_ontology_term_id
grade
cell_type_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Cancer Epithelial24489 cells Normal Epithelial4355 cells Endothelial ACKR14611 cells Cancer Basal SC4312 cells PVL Differentiated3487 cells CAFs myCAF-like3420 cells CAFs MSC iCAF-like3153 cells Luminal Progenitors1992 cells Endothelial CXCL121644 cells Cycling T-cells1528 cells Endothelial RGS51147 cells Endothelial Lymphatic LYVE1203 cells T_cells_c1_CD4+_IL7R7786 cells T_cells_c4_CD8+_ZFP365063 cells T_cells_c0_CD4+_CCR74952 cells Endothelial ACKR14611 cells Cancer Basal SC4312 cells T_cells_c2_CD4+_T-regs_FOXP34246 cells PVL Differentiated s33487 cells T_cells_c7_CD8+_IFNG3168 cells CAFs MSC iCAF-like s12309 cells CAFs myCAF like s52265 cells T_cells_c3_CD4+_Tfh_CXCL132247 cells Myeloid_c10_Macrophage_1_EGR12150 cells Myeloid_c1_LAM1_FABP52122 cells Luminal Progenitors1992 cells T_cells_c8_CD8+_LAG31955 cells T_cells_c9_NK_cells_AREG1846 cells Endothelial CXCL121644 cells T_cells_c11_MKI671528 cells Myeloid_c12_Monocyte_1_IL1B1339 cells PVL Immature s11169 cells Endothelial RGS51147 cells Myeloid_c2_LAM2_APOE1126 cells T_cells_c10_NKT_cells_FCGR3A1122 cells T_cells_c6_IFIT11017 cells Myeloid_c8_Monocyte_2_S100A9935 cells CAFs MSC iCAF-like s2844 cells CAFs myCAF like s4602 cells CAFs Transitioning s3553 cells Myeloid_c9_Macrophage_2_CXCL10505 cells Myeloid_c11_cDC2_CD1C337 cells Myeloid_c4_DCs_pDC_IRF7331 cells T_cells_c5_CD8+_GZMK284 cells Endothelial Lymphatic LYVE1203 cells Myeloid_c3_cDC1_CLEC9A156 cells Myeloid_c0_DC_LAMP3131 cells Myeloid_c7_Monocyte_3_FCGR3A54 cells Myeloid_c5_Macrophage_3_SIGLEC126 cells no_gene_module75575 cells no_scTYPER_call75575 cells no_inferCNV_call71220 cells Cryopreserved_chunk36207 cells HsapDv:000014110984 cells HsapDv:000014310339 cells Neoadjuvant AC (4x), Paclitaxel (3x)5619 cells Neoadjuvant FEC-D4451 cells AC, Paclitaxel, Herceptin (administered for Dx 3 years prior)3527 cells Neoadjuvant AC (4x), Paclitaxel (1x)1754 cells NCBITaxon:9606100064 cells UBERON:0000310100064 cells MONDO:0004989100064 cells CD4-positive, alpha-beta T cell19231 cells luminal epithelial cell of mammary gland14367 cells mammary gland epithelial cell13379 cells CD8-positive, alpha-beta T cell11487 cells endothelial cell7402 cells fibroblast of breast6573 cells natural killer cell1846 cells mature NK T cell1122 cells myoepithelial cell of mammary gland1098 cells endothelial cell of lymphatic vessel203 cells breast carcinoma100064 cells 47-year-old human stage10984 cells 49-year-old human stage10339 cells 55-year-old human stage8609 cells 63-year-old human stage7985 cells 52-year-old human stage6979 cells 43-year-old human stage6178 cells 88-year-old human stage5789 cells 73-year-old human stage5619 cells 41-year-old human stage5309 cells 42-year-old human stage4409 cells 67-year-old human stage4149 cells 85-year-old human stage3764 cells 58-year-old human stage3585 cells 61-year-old human stage3527 cells 60-year-old human stage3024 cells 57-year-old human stage2531 cells 82-year-old human stage2327 cells 54-year-old human stage2195 cells 35-year-old human stage2131 cells 50-year-old human stage631 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/dea97145-f712-431c-a223-6b5f565f362a
Alias names
GSE176078, EGAS00001005173, SCP1039, PMID34493872, PMC9044823
Cite this study
Wu, S.Z., Al-Eryani, G., Roden, D.L., Junankar, S., Harvey, K., Andersson, A., Thennavan, A., Wang, C., Torpy, J.R., Bartonicek, N. and Wang, T., 2021. A single-cell and spatially resolved atlas of human breast cancers. Nature genetics, 53(9), pp.1334-1347. https://doi.org/10.1038/s41588-021-00911-1
