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The role of Rho GTPases in hematopoietic stem cell biology: RhoA GTPase regulates adult HSC engraftment and Rac1 GTPases is important for embryonic HSC migration

Ghiaur, Gabriel
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204374567

Abstract Details

2008, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Two closely related Rho GTPases (Rac1 and RhoA) that influence basic biological functions of hematopoietic stem cells were studied during the work included in this thesis. In Chapter 2, using retroviral-mediated gene transfer to express a DN mutant of RhoA, we establish RhoA as a potential important regulator of hematopoietic reconstitution after stem cell transplantation. By controlling adhesion and migration and, in particular, cell cycle progression, we demonstrate dramatically enhanced serial transplantation of transduced and DN RhoA-expressing hematopoietic stem cells and from these data postulate that RhoA may prove to be a novel molecular target for augmentation of hematopoietic stem cell engraftment. In Chapter 3, using lineage-specific conditional gene targeting, we establish Rac1 as a critical regulator of migration of hematopoietic stem and progenitor cells during embryonic development. The experimental design afforded us the opportunity to elucidate in more detail the events surrounding the initiation of definitive hematopoiesis in mammals. Without Rac1, definitive hematopoietic stem and progenitor cells from yolk sac fail to seed the fetal liver and intra-embryonic anatomic sites of hematopoiesis. Given the ongoing controversy in the field in this regard, these findings are particularly important and add more support to the hypothesis that definitive hematopoiesis in the adult mouse is derived from yolk sac at large. These findings also offer conclusive additional evidence that Rho GTPases (RhoA and Rac1) regulate hematopoietic stem cell functions in multiple ways during both adult and embryonic hematopoiesis. At the same time, the studies presented here set the stage for new inquires into the molecular mechanism controlling adult and fetal hematopoietic stem cell biology.
David Williams, MD (Committee Chair)
Christopher Wiley, PhD (Committee Member)
James Lessard, PhD (Committee Member)
Mervin Yoder, MD (Committee Member)
Yi Zheng, PhD (Committee Member)
138 p.
Molecular Biology
Hematopoietic stem cell; Hematopoietic ontogeny; yolk sac; AGM; Fetal Liver; Bone marrow transplantation; gene therapy; Rho GTPase; Rac; RhoA

Recommended Citations

Citations

  • Ghiaur, G. (2008). The role of Rho GTPases in hematopoietic stem cell biology: RhoA GTPase regulates adult HSC engraftment and Rac1 GTPases is important for embryonic HSC migration [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204374567

    APA Style (7th edition)

  • Ghiaur, Gabriel. The role of Rho GTPases in hematopoietic stem cell biology: RhoA GTPase regulates adult HSC engraftment and Rac1 GTPases is important for embryonic HSC migration. 2008. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204374567.

    MLA Style (8th edition)

  • Ghiaur, Gabriel. "The role of Rho GTPases in hematopoietic stem cell biology: RhoA GTPase regulates adult HSC engraftment and Rac1 GTPases is important for embryonic HSC migration." Doctoral dissertation, University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204374567

    Chicago Manual of Style (17th edition)

ucin1204374567
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© 2008, some rights reserved.Creative Commons License The role of Rho GTPases in hematopoietic stem cell biology: RhoA GTPase regulates adult HSC engraftment and Rac1 GTPases is important for embryonic HSC migration by Gabriel Ghiaur is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.