Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK.
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
Nat Commun. 2017 Dec 11;8(1):2128. doi: 10.1038/s41467-017-02001-5.
Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells-especially in the luminal compartment-should rather be conceptualised as being part of a continuous spectrum of differentiation. Furthermore, our data support the existence of a common luminal progenitor cell giving rise to intermediate, restricted alveolar and hormone-sensing progenitors. This luminal progenitor compartment undergoes transcriptional changes in response to a full pregnancy, lactation and involution. In summary, our results provide a global, unbiased view of adult mammary gland development.
描述乳腺上皮细胞（MEC）的层次结构以及它们在成年发育过程中的调控方式对于理解乳腺癌的发生机制非常重要。在这里，我们报告了使用单细胞 RNA 测序来确定 MEC 在四个发育阶段（未孕、中期妊娠、哺乳期和产后退化期）的基因表达谱。我们对 23184 个细胞进行的分析确定了 15 个簇，其中很少有簇可以仅用一个标记基因来完全描述。相反，我们认为上皮细胞 - 尤其是腔室中的上皮细胞 - 应该被视为连续分化谱的一部分。此外，我们的数据支持存在一个共同的腔室祖细胞，该祖细胞产生中间、限制的肺泡和激素感应祖细胞。这个腔室祖细胞在经历完整的妊娠、哺乳和退化时会发生转录变化。总之，我们的结果提供了对成年乳腺发育的全面、无偏的观察。
