Department of Cell Biology, Harvard Medical School (HMS), Boston, MA 02115, USA.
Department of Cell Biology, Harvard Medical School (HMS), Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, MA 02115, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Dev Cell. 2022 Jun 6;57(11):1400-1420.e7. doi: 10.1016/j.devcel.2022.05.003. Epub 2022 May 25.
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,其对生理和病理生理条件的反应改变了其疾病易感性,但这些临床变量对细胞状态的具体影响仍未得到充分注释。我们通过整合单细胞 RNA 测序、质谱细胞术和周期性免疫荧光技术,呈现了一个统一的、高分辨率的乳房图谱,涵盖了无数的状态。我们在肺泡、激素感应和基底上皮谱系内定义了细胞亚型,描绘了几个亚型与癌症风险因素(包括年龄、产次和 BRCA2 种系突变)的关联。特别值得关注的是一组被称为基底-腔(BL)细胞的肺泡细胞,它们表现出较差的转录谱系保真度,随年龄增长而积累,并带有与基底样乳腺癌相关的基因特征。我们进一步利用培养基耗竭方法来鉴定调节类器官中细胞亚型比例的分子因素。这些数据是一个丰富的资源,可以阐明不同的乳腺细胞状态。
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