Pellacani Davide, Bilenky Misha, Kannan Nagarajan, Heravi-Moussavi Alireza, Knapp David J H F, Gakkhar Sitanshu, Moksa Michelle, Carles Annaick, Moore Richard, Mungall Andrew J, Marra Marco A, Jones Steven J M, Aparicio Samuel, Hirst Martin, Eaves Connie J
Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Cell Rep. 2016 Nov 15;17(8):2060-2074. doi: 10.1016/j.celrep.2016.10.058.
The normal adult human mammary gland is a continuous bilayered epithelial system. Bipotent and myoepithelial progenitors are prominent and unique components of the outer (basal) layer. The inner (luminal) layer includes both luminal-restricted progenitors and a phenotypically separable fraction that lacks progenitor activity. We now report an epigenomic comparison of these three subsets with one another, with their associated stromal cells, and with three immortalized, non-tumorigenic human mammary cell lines. Each genome-wide analysis contains profiles for six histone marks, methylated DNA, and RNA transcripts. Analysis of these datasets shows that each cell type has unique features, primarily within genomic regulatory regions, and that the cell lines group together. Analyses of the promoter and enhancer profiles place the luminal progenitors in between the basal cells and the non-progenitor luminal subset. Integrative analysis reveals networks of subset-specific transcription factors.
正常成年人类乳腺是一个连续的双层上皮系统。双能和肌上皮祖细胞是外层（基底）层突出且独特的组成部分。内层（管腔）层包括管腔限制性祖细胞和一个缺乏祖细胞活性但在表型上可分离的部分。我们现在报告这三个亚群彼此之间、与它们相关的基质细胞以及与三种永生化、非致瘤性人类乳腺细胞系的表观基因组比较。每个全基因组分析都包含六种组蛋白标记、甲基化DNA和RNA转录本的图谱。对这些数据集的分析表明，每种细胞类型都有独特的特征，主要在基因组调控区域内，并且细胞系聚集在一起。对启动子和增强子图谱的分析将管腔祖细胞置于基底细胞和非祖细胞管腔亚群之间。综合分析揭示了亚群特异性转录因子网络。
