A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells.
Cell Rep Med
; 2(3): 100219, 2021 03 16.
Article
em En
| MEDLINE
| ID: mdl-33763657
ABSTRACT
Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid tissue collection/processing protocol to perform scRNA-seq of breast biopsies of healthy women and identify 23 breast epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters are applied to analyze transcriptomes of ~3,000 breast cancers. Gene signatures derived from mature luminal cell clusters are enriched in ~68% of breast cancers, whereas a signature from a luminal progenitor cluster is enriched in ~20% of breast cancers. Overexpression of luminal progenitor cluster-derived signatures in HER2+, but not in other subtypes, is associated with unfavorable outcome. We identify TBX3 and PDK4 as genes co-expressed with estrogen receptor (ER) in the normal breasts, and their expression analyses in >550 breast cancers enable prognostically relevant subclassification of ER+ breast cancers.
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MEDLINE
Assunto principal:
Neoplasias da Mama
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Receptor ErbB-2
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Linhagem da Célula
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Proteínas com Domínio T
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Receptor alfa de Estrogênio
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Células Epiteliais
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Piruvato Desidrogenase Quinase de Transferência de Acetil
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article