[PDF][PDF] A human breast atlas integrating single-cell proteomics and transcriptomics

GK Gray, CMC Li, JM Rosenbluth, LM Selfors… - Developmental cell, 2022 - cell.com
GK Gray, CMC Li, JM Rosenbluth, LM Selfors, N Girnius, JR Lin, RCJ Schackmann, WL Goh
Developmental cell, 2022cell.com
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 …
Summary
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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