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着细胞的命运。我们利用乳腺模型系统，研究未分化的乳腺上皮干细胞和祖细胞（能够形成乳腺的所有上皮细胞）分化到最终规范的乳分泌细胞的过程。我们使用一种新颖的多学科方法来研究干细胞功能，该方法结合了干细胞和祖细胞的富集和新型培养，并在体内干细胞试验中对其进行评估。我们的研究在基因阵列筛选中发现了一个新的乳腺上皮分化的关键调节因子，用于调节发育的基因。我们还有其他候选者在等待鉴定。总之，我们提出了一种机制，即未分化乳腺上皮干细胞的上游信号建立了一个允许的微环境，在这个微环境中，最终的功能分化和生存控制是由催乳素调节的。催乳素是乳腺发育所必需的肽激素。我们还发现了两个催乳素调节基因，交替控制细胞存活或凋亡。我们假设它们调节着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可以促进存活，还可以使细胞敏感，以应对即将发生的催乳素反应细胞的破坏。我们的工作将提供对控制干细胞分化和细胞存活的分子控制的理解，使用一个非常适合这项研究的组织发育模型。为了了解组织发育、组织再生甚至癌症，了解这些功能是至关重要的。

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 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.