The current research in my lab is focused on understanding the origins of the blood system in embryonic development. In adult mammals, all blood lineages including red blood cells, platelets, and the cells of the innate and adaptive immune systems are all derived from a single adult stem cell type, the blood-forming or hematopoietic stem cell (HSC). HSCs continuously produce downstream progeny to repopulate the blood system and maintain homeostasis. In the embryo, blood development occurs in a series of waves, in which the functional properties that define HSCs gradually emerge with each successive wave. Understanding the relationship between each blood wave, and the molecular processes that guide their maturation is the primary goal of my research. We have identified a population of cells in the mouse embryo that are potentially precursors to HSCs. My previous work determined that these cells are multipotent, capable of giving rise to all blood lineages. Our work now focuses on establishing the in vivo potential of these cells to establish them as bona fide precursors to HSCs. Our candidate HSC precursors are found in many tissues in the developing embryo. However, because these cells are in circulation, it remains unclear from which tissue(s) they originate. We have performed extensive gene expression analysis of these precursors, and identified unique molecular signatures that we can use to perform lineage tracing analyses in mice to determine from which tissues these precursors originate. Our work in mouse models will greatly inform us of the molecular processes by which HSCs emerge in embryogenesis. We will apply this knowledge to humans by manipulating development in pluripotent stem cell lines to generate HSCs or their precursors, which we will functionally test both in vitro and in vivo.
2010 Gross Hall
1100 Gross Hall