An important objective in regenerative medicine is to make hematopoietic stem cells (HSCs) from embryonic or induced pluripotent stem cells (ESCs or iPSCs). HSCs differentiate from a small population of endothelial cells in the embryo called hemogenic endothelium. The differentiation of HSCs from hemogenic endothelium involves an intermediate step in which blood cells accumulate in the major vasculature as pre-HSCs before being released into the circulation to colonize the fetal liver, where the pre-HSCs mature into fully functional HSCs. We plan to profile the gene expression and epigenetic changes that occur during the transitions between embryonic pre-HSCs, an intermediate population that we call HSC explant (HSCex), and fetal liver HSCs. We will also analyze differentially expressed cell surface markers for their utility in purifying embryonic HSCs. The project involves collaboration between a developmental biologist and a bioinformatician.
Bone marrow transplantation is a life-saving procedure for many patients with malignant and nonmalignant hematologic disease, including immune deficiency. Unfortunately not every patient has a suitable donor. The ability to produce HSCs from patient-derived iPS cells would solve this problem. We believe that understanding how HSCs form in the embryo, and having landmarks that will allow us to identify HSCs at various stages of formation is necessary if we are to successfully produce them in vitro.
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