Please use this identifier to cite or link to this item:
https://hdl.handle.net/20.500.12202/382
Title: | Transcription Factors Associated with Gamma-globin Expression in Human Adult Definitive Erythropoiesis Before and After Induction by Hydroxyurea |
Authors: | Grieco, Amanda J. |
Keywords: | Molecular biology. Aeronomy. Cellular biology. |
Issue Date: | 2016 |
Publisher: | ProQuest Dissertations & Theses |
Citation: | Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.;Advisors: Eric E. Bouhassira. |
Abstract: | The molecular mechanisms governing gamma-globin expression in a subset of fetal hemoglobin (alpha2:gamma2; HbF) expressing red blood cells (F-cells) and the mechanisms underlying the variability of response to hydroxyurea induced gamma-globin expression in the treatment of sickle cell disease are not completely understood. To explore molecular differences in these conditions, a serum-free in vitro culture system suitable for large scale production of erythroblasts derived from primary human hematopoietic progenitors is optimized. The culture system recapitulates steady-state adult erythropoiesis and can support erythroid differentiation with the addition of cytotoxic hydroxyurea. Using this system, intra-person clonal populations of erythroblasts derived from bone marrow common myeloid progenitors were evaluated for molecular factors associated with gamma-globin expression. Data demonstrate that the level of fetal hemoglobin produced in F-cells negatively correlates with expression of BCL11A, KLF1 and TALL With the addition of hydroxyurea, successful induction of gamma-globin includes a further reduction in BCL11 A, KLF1 and TALI expression along with a decrease in SOX6 expression. These data suggests that expression changes in this transcription factor network modulate gamma-globin expression in F-cells during steady state erythropoiesis and after induction with hydroxyurea. |
URI: | https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:10143429 https://hdl.handle.net/20.500.12202/382 |
Appears in Collections: | Albert Einstein College of Medicine: Doctoral Dissertations |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.