Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.
Sci Rep. 2016 Nov 3;6:35810. doi: 10.1038/srep35810.
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages. Using RNA-seq, we show that basal cells are extraordinarily transcriptionally dynamic throughout pregnancy when compared to luminal cells. We identified gene expression changes that define specific basal functions acquired during development that led to the identification of novel markers. Enrichment analysis of gene sets from 24 mouse models for breast cancer pinpoint to a potential new function for insulin-like growth factor 1 (Igf1r) in the basal epithelium during lactogenesis. We establish that β-catenin signaling is activated in basal cells during early pregnancy, and demonstrate that this activity is mediated by lysophosphatidic acid receptor 3 (Lpar3). These findings identify novel pathways active during functional maturation of the adult mammary gland.
在妊娠期间,成年乳腺的腔上皮细胞和基底上皮细胞增殖和分化,导致成年乳腺的重塑。虽然已经在整个腺体中描述了控制这一过程的途径,但特定细胞亚型的贡献,特别是基底隔室,在很大程度上仍然未知。基底细胞提供结构和收缩支持,但它们也在所有发育阶段协调基质与腔室之间的通讯。通过 RNA-seq,我们发现与腔上皮细胞相比,基底细胞在整个妊娠期间具有极高的转录动态性。我们确定了定义在发育过程中获得的特定基底功能的基因表达变化,从而鉴定出了新的标记物。对 24 种乳腺癌小鼠模型的基因集富集分析表明,胰岛素样生长因子 1(Igf1r)在泌乳期的基底上皮中可能具有新的功能。我们证实,β-连环蛋白信号在妊娠早期在基底细胞中被激活,并证明这种活性是由溶血磷脂酸受体 3(Lpar3)介导的。这些发现确定了成年乳腺功能成熟过程中活跃的新途径。