This work focuses on the development and function of hematopoietic cells. First, this work identifies a novel marker CD11a, which distinguishes various tissue resident macrophage populations from bone-marrow derived cells that may colonize a tissue during inflammation. In the context of Alzheimer’s disease, it is determined that myeloid cells that cluster around amyloid plaques are actually brain resident microglia, not infiltrating peripheral macrophages. Using CD11a, a novel quantification technique is also described, which demonstrated microglia proliferation and increased T cells infiltration in the AD mice. Additionally, we outline how CD11a expression patterns in various tissue resident macrophage (trMac) populations may help determine the developmental relationships between these cells. We corroborate other studies that microglia in the brain and Langerhans cells in the skin come from erythro-myeloid progenitors that arise in the embryonic yolk sac (YS). Additionally, we also provide evidence that some hematopoietic stem cells also arise from the mesoderm in extra-embryonic tissue, such as the YS, placenta as well as the vitelline vessels. Using the HoxB6-CreER lineage tracing system, we demonstrate that YS hematopoiesis is critical not just for trMacs, but also for HSC development.