Published:May 25, 2022DOI:https://doi.org/10.1016/j.devcel.2022.05.003
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.
乳房是一个动态的器官，它对生理和病理生理条件的反应改变了它的疾病易感性，然而这些临床变量对细胞状态的具体影响仍然没有得到很好的注释。我们通过整合单细胞RNA-seq、大规模细胞术和循环免疫荧光，提出了一个统一的、高分辨率的乳腺图谱，包括了无数的状态。我们在肺泡、激素感应和基底上皮系中定义了细胞亚型，划定了几个亚型与癌症风险因素的关系，包括年龄、生育率和BRCA2种系突变。特别值得关注的是被称为基底腔（BL）细胞的肺泡细胞亚群，它们表现出较差的转录系保真度，随着年龄的增长而积累，并带有与基底样乳腺癌相关的基因特征。我们进一步利用介质耗竭的方法来确定调节器官中细胞亚型比例的分子因素。总之，这些数据是阐明不同乳腺细胞状态的丰富资源。
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