Control of mRNA Translation in Erythropoiesis
Year: 2007
Type: dissertation
Abstract: The balance between proliferation and differentiation of committed \nhematopoietic progenitors is under tight control to maintain the progenitor pool and \nensure maturation in response to physiological demand. Whereas development of the \ndifferent hematopoietic lineages requires the coordinate expression of transcription \nfactors, the balance between proliferation and differentiation is controlled by growth \nfactors. These include cytokines such as erythropoietin (Epo) and granulocyte-colony \nstimulating factor (G-CSF) required for differentiation into specific lineages, as well \nas growth factors that enhance proliferation and delay differentiation of progenitors \nsuch as stem cell factor (SCF) and the ligand for FMS-like tyrosine kinase 3 (Flt3-\nligand). \n\nTo investigate how the balance between expansion and differentiation of \nerythroid progenitors is controlled by growth factors, we used a model in which \nerythroid progenitors proliferate in the presence of Epo, SCF and glucocorticoids \nwhile they maintain the capacity to differentiate upon addition of Epo alone. SCF-\ndriven proliferation and inhibition of differentiation is dependent on phosphoinositide-\n3-kinase (PI3K) activation. The main objective of the study described in this thesis is \nto understand how PI3K-controlled gene expression regulates the balance between \nproliferation and differentiation of erythroid progenitors. In particular, we studied the \nrole of PI3K dependent control of mRNA translation.
Author: Godfrey Grech
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1512890526