A human breast atlas integrating single-cell proteomics and transcriptomics

G. Kenneth Gray, Carman Man-Chung Li, Jennifer M. Rosenbluth, Laura M. Selfors, Nomeda Girnius, Jia-Ren Lin, Ron C.J. Schackmann, Walter L. Goh, Kaitlin Moore, Hana K. Shapiro, Shaolin Mei, Kurt D’Andrea, Katherine L. Nathanson, Peter K. Sorger, Sandro Santagata, Aviv Regev, Judy E. Garber, Deborah A. Dillon, Joan S. Brugge

Abstract

The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation. Of particular interest is a subset of alveolar cells termed basal-luminal (BL) cells, which exhibit poor transcriptional lineage fidelity, accumulate with age, and carry a gene signature associated with basal-like breast cancer. We further utilize a medium-depletion approach to identify molecular factors regulating cell-subtype proportion in organoids. Together, these data are a rich resource to elucidate diverse mammary cell states.

Datasets

1. Single-Cell RNA Sequencing of Breast Tissues: Cell Subtypes and Cancer Risk Factors
Metadata
donor_id
genotype_1
Phase
surgeryType
menopause
numberOfPregnancies
numberOfBirths
gravidityParity
cellSubtype
ParticipantID
organism_ontology_term_id
tissue_ontology_term_id
assay_ontology_term_id
cell_type_ontology_term_id
self_reported_ethnicity_ontology_term_id
development_stage_ontology_term_id
sex_ontology_term_id
suspension_type
disease_ontology_term_id
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
Human-BRCA1-B7527 cells
Human-WT-B7130 cells
Human-BRCA1-E7128 cells
Human-BRCA1-H5101 cells
Human-BRCA1-C4965 cells
Human-WT-A4749 cells
Human-WT-D4458 cells
Human-WT-C3025 cells
Human-BRCA2-A2983 cells
Human-BRCA1-G1497 cells
Human-BRCA1-D1486 cells
Human-BRCA2-C1029 cells
Human-BRCA2-B507 cells
Human-BRCA2-E438 cells
Human-BRCA2-F436 cells
Human-BRCA2-D222 cells
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A human breast atlas integrating single-cell proteomics and transcriptomics

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Source data

https://cellxgene.cziscience.com/collections/99f1515b-46a2-4bc4-94c3-f62659dc1eb4

Alias names

GSE180878, SCP1731, syn26560310, PMID35617956, PMC9202341

Cite this study

Gray, G.K., Li, C.M.C., Rosenbluth, J.M., Selfors, L.M., Girnius, N., Lin, J.R., Schackmann, R.C., Goh, W.L., Moore, K., Shapiro, H.K. and Mei, S., 2022. A human breast atlas integrating single-cell proteomics and transcriptomics. Developmental cell, 57(11), pp.1400-1420. https://doi.org/10.1016/j.devcel.2022.05.003