Mammary gland biology: differentiation and development

在组织发育过程中，控制上皮细胞分化（特化）和存活的基因和蛋白质控制细胞命运。我们使用乳腺的模型系统来研究从未分化的乳腺上皮干细胞和祖细胞（能够形成腺体的所有上皮细胞）到乳汁分泌细胞的最终规格的分化过程。我们使用一种新的，多学科的方法来研究干细胞和祖细胞的功能，结合了富集和新的干细胞和祖细胞的培养，在体内干细胞检测评估。我们的研究确定了一个新的关键调节乳腺上皮细胞分化的基因阵列筛选基因调控发展。我们还有更多的候选人等待鉴定。总的来说，我们提出了一种机制，在未分化的乳腺上皮干细胞的上游信号建立一个允许的微环境中，最终的功能分化和控制的生存是由催乳素调节。催乳素是乳腺发育所必需的肽类激素。我们还确定了两个催乳素调节基因，交替控制细胞存活或凋亡。我们推测它们调节乳腺中从存活到凋亡的转换。我们认为，催乳素调节的靶基因不仅促进生存，但也可以敏感的细胞催乳素反应细胞的即将发生的断奶破坏。我们的工作将提供一个了解的分子控制管理干细胞分化和细胞存活，使用组织发育模型，是非常适合这项调查。了解这些功能对于了解组织发育，组织再生甚至癌症至关重要。

Genes and proteins that control epithelial cell differentiation (specialization) and survival control cell fate during tissue development. We use the model system of the mammary gland to study the process of differentiation from undifferentiated mammary epithelial stem and progenitor cells (capable of forming all the epithelial cells of the gland) to the final specification of the milk secretory cells. We use a novel, multidisciplinary approach to study stem and progenitor cell function that combines the enrichment and novel culture of stem and progenitor cells, with their assessment in an in vivo stem cell assay. Our research identified a new key regulator of mammary epithelial differentiation in a gene-array screen for genes that regulate development. We have additional candidates awaiting characterization. Overall, we propose a mechanism by which upstream signals in undifferentiated mammary epithelial stem cells establish a permissive microenvironment in which final functional differentiation and control of survival is regulated by prolactin. Prolactin is a peptide hormone essential for mammary gland development. We also identified two prolactin-regulated genes that alternatively control cell survival or apoptosis. We hypothesize that they regulate the switch from survival to apoptosis in the mammary gland. We believe that prolactin regulated target genes not only promote survival but alternatively can sensitize the cells for the imminent destruction of prolactin-responsive cells that occurs with weaning. Our work will provide an understanding of the molecular controls governing stem cell differentiation and cell survival, using a tissue development model that is perfectly suited for this investigation. It is essential to understand these functions in order to understand tissue development, tissue regeneration and even cancer.