Mammary gland biology - differentiation and development

点击翻译按钮获取中文摘要

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 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.