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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:563966 |
| Date | January 2012 |
| Creators | Sheriff, Lozan |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/3823/ |
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