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

dc.contributor.authorJackson, Carlo Stephan
dc.contributor.authorDurandt, Chrisna
dc.contributor.authorJanse van Rensburg, IIse
dc.contributor.authorPraloran, Vincent
dc.contributor.authorDe la Grange, Philippe Brunet
dc.contributor.authorPepper, Michael Sean
dc.contributor.emailmichael.pepper@up.ac.zaen_ZA
dc.date.accessioned2017-08-15T09:49:20Z
dc.date.available2017-08-15T09:49:20Z
dc.date.issued2017-05
dc.description.abstractCulture 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.departmentBiochemistryen_ZA
dc.description.departmentImmunologyen_ZA
dc.description.sponsorshipThe 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.urihttp://www.elsevier.com/locate/scren_ZA
dc.identifier.citationJackson, 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.issn1873-5061 (print)
dc.identifier.issn1876-7753 (online)
dc.identifier.other10.1016/j.scr.2017.04.007
dc.identifier.urihttp://hdl.handle.net/2263/61652
dc.language.isoenen_ZA
dc.publisherElsevieren_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.subjectStemregenin 1en_ZA
dc.subjectHematopoietic stem (HSC)en_ZA
dc.subjectProgenitor cells (HPC)en_ZA
dc.subjectStem cell expansionen_ZA
dc.subjectAryl hydrocarbon receptor nuclear translocator complexen_ZA
dc.subjectDimethyloxaloylglycine (DMOG)en_ZA
dc.titleTargeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansionen_ZA
dc.typeArticleen_ZA

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