A human breast atlas integrating single-cell proteomics and transcriptomics.
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A human breast atlas integrating single-cell proteomics and transcriptomics.

Gray, G Kenneth;Li, Carman Man-Chung;Rosenbluth, Jennifer M;Selfors, Laura M;Girnius, Nomeda;Lin, Jia-Ren;Schackmann, Ron C J;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;
Developmental cell 2022 Vol. 57 pp. 1400-1420.e7
93
gray2022adevelopmental

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.

Keywords

Breast cancer aging brca1 scrna-seq brca2 organoids cytof mass cytometry cell state plasticity mammary biology multi-omic single-cell atlas multiplexed tissue staining

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DOI:
10.1016/j.devcel.2022.05.003

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ID: 277019
Ref Key: gray2022adevelopmental
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