학술논문
A human breast atlas integrating single-cell proteomics and transcriptomics
Document Type
article
Author
Gray, G Kenneth; Li, Carman Man-Chung; Rosenbluth, Jennifer M; Selfors, Laura M; Girnius, Nomeda; Lin, Jia-Ren; Schackmann, Ron CJ; Goh, Walter L; Moore, Kaitlin; Shapiro, Hana K; Mei, Shaolin; D'Andrea, Kurt; Nathanson, Katherine L; Sorger, Peter K; Santagata, Sandro; Regev, Aviv; Garber, Judy E; Dillon, Deborah A; Brugge, Joan S
Source
Developmental Cell. 57(11)
Subject
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.