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
Year: 2008
Type: article
Abstract: 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 lineagespecific 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.
Author: Gabriel Ghiaur
Institution: University of Cincinnati
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2518387632