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

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ID: 277019
2022
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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.
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Authors G Kenneth Gray, Carman Man-Chung Li, Jennifer M Rosenbluth, Laura M Selfors, Nomeda Girnius, Jia-Ren Lin, Ron C J Schackmann, Walter L Goh, Kaitlin Moore, Hana K Shapiro, Shaolin Mei, Kurt D'Andrea, Katherine L Nathanson, Peter K Sorger, Sandro Santagata, Aviv Regev, Judy E Garber, Deborah A Dillon, Joan S Brugge
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Journal Developmental cell
Year 2022
DOI
10.1016/j.devcel.2022.05.003
URL
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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