Hematopoietic stem cells (HSCs) are multi-potent cells that typically reside in the bone marrow (BM) and are capable of differentiating to repopulate the entire spectrum of blood cells. HSCs in the bone marrow have four cellular fates; it can self-renew, differentiate, undergo apoptosis, and/or mobilize out of the BM microenvironment and egress into the peripheral blood. The purpose of my Ph.D. thesis dissertation is to study the developmental potential of murine HSC and its ability to mobilize, differentiate, and self renew. Mobilization involves the use of chemotherapeutic agents and/or cytokines to harness an organism's physiological release of HSC into the peripheral blood. Increasing the number of HSCs in the peripheral blood allows for subsequent collection and transplantation. Using the murine model, I studied the effects of mobilizing reagents on the dynamic cellular and functional changes of BM-HSC. Further, while characterizing the intrinsic changes to HSC properties upon mobilization induction, I also identified potential molecular proteins that can be used to improve the homing and engraftment of HSC after transplantation. With the insights I have gained into mobilized HSC biology, as well as preliminary studies involving HSC trans-differentiation and self-renewal regulation, the framework has been laid for future studies into hematopoietic stem cell manipulation and regulation.
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