Stem cells are essential for animal development and allow the maintenance and regeneration of tissues. Stem cells retain the capability to divide and to develop into many types of adult cells throughout the lifetime of an organism. The blood stem cells in humans and animals are particularly important for fighting infections as they produce the immune cells required to fight infection. The work we propose seeks to understand the mechanisms that regulate the activation of blood stem cells such that they produce immune cells upon infection. Our work focuses on the role played by the blood stem cell's environment in regulating this transition. In particular we will focus on the role of various cell junctions in shaping the signals that control stem cell behavior. We propose that in response to infection the stem cell environment changes in very specific ways and that this induces the activation of blood stem cells. Understanding the mechanisms that induce blood stem cell activation upon infection will help us gain insight into what happens in diseases that affect the blood stem cell niche such as leukemia and autoimmune diseases.