Informace o publikaci

Haematopoiesis in vitro under HIF-1 modulation



Rok publikování 2013
Druh Další prezentace na konferencích
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Popis Induction and progression of haematopoiesis is under both direct and indirect control of hypoxia through modulation of hypoxia inducible factors (HIF). Here we focus on the role of HIF family member HIF-1alpha in regulation of haematopoiesis. We have observed that depletion of HIF-1alpha accelerates haematopoiesis in embryonic stem cells in vitro. In mutated cells both BFU-E and CFU-E appears earlier and pro haematopoietic gene expressions are increased compared to wild-type cells. Recently it has been observed that deferoxamine (DFO) and other Fe ions chelators not only induce differentiation but also shift myeloid differentiation to monocyte lineage in acute myeloid leukaemia (Callens et al., 2010). DFO through Fe ion chelation also stabilizes HIF-1. Therefore we tested the effect of classical HIF stabilizing drugs (CoCl2 and DMOG) on adult and fetal haematopoiesis in vitro. In accordance with the effect of HIF-1alpha depletion, addition of CoCl2 to the culture reduced erythropoiesis (decreased number of BFU-E and CFU-E) in both adult (bone marrow-derived) and fetal (fetal liver-derived) hematopoietic progenitors. Interestingly, CoCl2 also decreased CFU-G together with CFU-GM but increased CFU-M number in fetal haematopoiesis in the same manner as DFO in acute myeloid leukaemia study (Callens et al., 2010). In contrast, in adult hematopoietic progenitors CoCl2 increased number of CFU-G and CFU-GM but decreased CFU-M. In summary, our results show HIF-1alpha dependent regulation of both overall haematopoiesis and myeloid lineage directed differentiation. Moreover, the results of myeloid differentiation in response to CoCl2 in adult and fetal haematopoiesis may indirectly support recent hypothesis, that tumor cells may have the phenotype of fetal progenitors rather than the phenotype of adult lineage progenitors. Callens C et al. (2010) J Exp Med. 207(4):731-50