학술논문

A human breast atlas integrating single-cell proteomics and transcriptomics
Document Type
article
Source
Developmental Cell. 57(11)
Subject
Biochemistry and Cell Biology
Biological Sciences
Breast Cancer
Cancer
Human Genome
Genetics
Aging
Biotechnology
Underpinning research
1.1 Normal biological development and functioning
Aetiology
2.1 Biological and endogenous factors
Animals
Breast
Breast Neoplasms
Female
Humans
Mammary Glands
Animal
Pregnancy
Proteomics
Transcriptome
BRCA1
BRCA2
CyTOF mass cytometry
aging
breast cancer
cell state plasticity
mammary biology
multi-omic single-cell atlas
multiplexed tissue staining
organoids
scRNA-Seq
Medical and Health Sciences
Developmental Biology
Biochemistry and cell biology
Language
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.