Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion

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dc.contributor.author Jackson, Carlo Stephan
dc.contributor.author Durandt, Chrisna
dc.contributor.author Janse van Rensburg, IIse
dc.contributor.author Praloran, Vincent
dc.contributor.author De la Grange, Philippe Brunet
dc.contributor.author Pepper, Michael Sean
dc.date.accessioned 2017-08-15T09:49:20Z
dc.date.available 2017-08-15T09:49:20Z
dc.date.issued 2017-05
dc.description.abstract Culture conditions used for the expansion of hematopoietic stemand progenitor cells (HSCs andHPCs, collectively HSPCs) should ideally favor the self renewal of long-termHSCs. At 20% O2, the synthesis of HIF-1α is balanced by its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by culturing CD34+cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl hydrocarbon receptor (AhR). The objective of this studywas to investigate howhypoxia,DMOG and Stemregenin 1might affect the expansion ofHSPCswith the aim of identifying optimal conditions for expansion in culture. It was found thatDMOG decreased proliferation but was effective in preserving the number of cells in the primitive hematopoietic subpopulations in vitro. The effect of DMOG was similar to hypoxia, although differenceswere observedwith regard to the side population and CD34+ sub-populations. Stemregenin 1 on the other hand increased the size of the primitive as well as the other HSC sub-populations. The use of Stemregenin 1 with DMOG increased the proportion of primitiveHSCs to 3.54% compared to 2.61% for Stemregenin 1 alone. In vivo engraftment studies confirmed these findings and showed that fewer cells (3710) are required for long-term engraftmentwhen HSCs are grown in Stemregenin 1 together with hypoxia than in Stemregenin 1 under conditions of normoxia (13430). en_ZA
dc.description.department Biochemistry en_ZA
dc.description.department Immunology en_ZA
dc.description.sponsorship The Medical Research Council of South Africa in terms of the MRC's Flagships Awards Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the SAMRC Extramural Unit for Stem Cell Research and Therapy, the Institute for Cellular and Molecular Medicine of the University of Pretoria, Etablissement Français du Sang, the University of Bordeaux fellowship, the German Academic Exchange Service and the National Research Foundation of South Africa (DAAD-NRF). en_ZA
dc.description.uri http://www.elsevier.com/locate/scr en_ZA
dc.identifier.citation Jackson, C.S., Durandt, C., Janse van Rensburg, I., Praloran, V., De la Grange, P.B. & Pepper, M.S. 2017, 'Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion', Stem Cell Research, vol. 21, pp. 124-131. en_ZA
dc.identifier.issn 1873-5061 (print)
dc.identifier.issn 1876-7753 (online)
dc.identifier.other 10.1016/j.scr.2017.04.007
dc.identifier.uri http://hdl.handle.net/2263/61652
dc.language.iso en en_ZA
dc.publisher Elsevier en_ZA
dc.rights © 2017 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). en_ZA
dc.subject Stemregenin 1 en_ZA
dc.subject Hematopoietic stem (HSC) en_ZA
dc.subject Progenitor cells (HPC) en_ZA
dc.subject Stem cell expansion en_ZA
dc.subject Aryl hydrocarbon receptor nuclear translocator complex en_ZA
dc.subject Dimethyloxaloylglycine (DMOG) en_ZA
dc.title Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion en_ZA
dc.type Article en_ZA


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