Use this URL to cite or link to this record in EThOS: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.563966 |
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Title: | Nuclear Factor κB transcriptional regulator function in haemopoietic stem cells | ||||||
Author: | Sheriff, Lozan |
ISNI:
0000 0004 2727 4554
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Awarding Body: | University of Birmingham | ||||||
Current Institution: | University of Birmingham | ||||||
Date of Award: | 2012 | ||||||
Availability of Full Text: |
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Abstract: | |||||||
The NF-κB family of transcription factors are essential for different stages of murine haemopoiesis as supported by studies on single or double knockout mice. The function of NF-κB1 and NF-κB2 in haemopoietic stem cells (HSCs) has never been described before. In mice, the bone marrow c-Kit+Sca1+Lin- (KSL) population represent HSCs that have the ability to repopulate the bone marrow of lethally irradiated animals. Using knockout mice technology we were able to study the function of NF-κB1 and NF-κB2 in HSCs by performing amongst others transplantation assays, which is the most precise way to test HSC potential. Nfκb1-/- KSL cells are fully able to reconstitute lethally irradiated recipients indicating that the in vivo self-renewal capacity is unaffected. In contrast, colony assays showed NF-κB1 dependency. Upon serial replating, knockout cells were not able to form colonies and lost their in vitro self-renewal capacity. Transplantation of the nfκb2-/- KSL cells engraft with a proliferative phenotype and a competitive advantage, with changes in the B-cell and myeloid cell lineages. Similar to nfκb1-/-, nfκb2-/- KSL cells lose their function as stem cells upon serial replating. These findings highlight the importance of NF-κB family proteins in HSCs, especially NF-κB2 and should be considered in the development of future cancer treatment that target NF-B proteins.
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Supervisor: | Not available | Sponsor: | Medical Research Council (MRC) | ||||
Qualification Name: | Thesis (Ph.D.) | Qualification Level: | Doctoral | ||||
EThOS ID: | uk.bl.ethos.563966 | DOI: | Not available | ||||
Keywords: | RK Dentistry | ||||||
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