A single‐cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast

To examine global changes in breast heterogeneity across different states, we determined the single‐cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1 +/– tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal Vol. 40; no. 11; pp. e107333 - n/a
Main Authors: Pal, Bhupinder, Chen, Yunshun, Vaillant, François, Capaldo, Bianca D, Joyce, Rachel, Song, Xiaoyu, Bryant, Vanessa L, Penington, Jocelyn S, Di Stefano, Leon, Tubau Ribera, Nina, Wilcox, Stephen, Mann, Gregory B, Papenfuss, Anthony T, Lindeman, Geoffrey J, Smyth, Gordon K, Visvader, Jane E
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.06.2021
Springer Nature B.V
John Wiley and Sons Inc
Subjects:
BRCA1 carriers
BRCA1 protein
Breast cancer
Breast Neoplasms - classification
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Carcinogenesis - genetics
Carcinogenesis - metabolism
Carcinogenesis - pathology
CD8 antigen
CD8-Positive T-Lymphocytes - metabolism
Clonal selection
Copy number
Cycles
EMBO03
EMBO19
EMBO22
ErbB-2 protein
Estrogen receptors
Estrogens
Female
Fibroblasts
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genetic Heterogeneity
Heterogeneity
Humans
Immunoregulation
Immunotherapy
Leukocyte migration
LN metastasis
Lymph nodes
Lymphatic system
Lymphocytes
Lymphocytes T
Macrophages
Mammary gland
Mammary glands
Mammary Glands, Human - cytology
Mammary Glands, Human - metabolism
Mammary Glands, Human - pathology
Menopause
Metastases
microenvironment
Microenvironments
Mutation
Preneoplasia
Receptors
Resource
RNA-Seq
Single-Cell Analysis
single‐cell RNA‐seq
Stroma
Transcriptomes
Tumor cells
Tumor Microenvironment
Tumors
microenvironment
single‐cell RNA‐seq
breast cancer
carriers
LN metastasis
single-cell RNA-seq
BRCA1 carriers
ISSN:0261-4189, 1460-2075, 1460-2075
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To examine global changes in breast heterogeneity across different states, we determined the single‐cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1 +/– tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post‐menopausal women. Single‐cell profiling of 34 treatment‐naive primary tumors, including estrogen receptor (ER) + , HER2 + , and triple‐negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1 +/– tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8 + T cells characterized triple‐negative and HER2 + cancers but not ER + tumors, while all subtypes comprised cycling tumor‐associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER + tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large‐scale integration of patient samples provides a high‐resolution map of cell diversity in normal and cancerous human breast. Synopsis To examine global changes in breast heterogeneity across different states, this gene expression resource integrates large‐scale patient samples from diverse tissue states and breast cancer subtypes, offering a refined high‐resolution map of cell diversity in the normal and cancerous human mammary gland. Single‐cell transcriptome analyses profile > 340,000 cells encompassing normal breast, preneoplastic BRCA1 +/– tissue, the major breast cancer subtypes, and metastatic lymph nodes. Pre‐ to post‐menopause transition is associated with marked stromal changes, with decreased PDGFRb and matrix‐associated genes in fibroblasts. Progression from preneoplasia to tumors correlates with increased immune infiltration in BRCA1 mutation carriers. Tumor epithelial compartments show comparable diversity in different breast cancer subtypes. Cycling CD8 + T‐cells are reduced in estrogen receptor (ER) + tumors, suggesting different immunoregulatory patterns. Both clonal selection and mass migration contribute to lymph node metastases in patients with ER + cancer. Graphical Abstract A large‐scale gene expression resource integrates diverse tissue samples and reveals unexpected heterogeneity of breast cancer subtypes.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors contributed equally to this work
These authors jointly supervised this work
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.15252/embj.2020107333