SI10 Effects of Hypoxia on the Proliferation and Differentiation Potential of Human Cord Blood‐ and Bone Marrow‐Derived Stem/Progenitor Cells

Umbilical cord blood (UCB) and bone marrow (BM)-derived stem and progenitor cells possess two characteristics required for successful tissue regeneration, which are extensive proliferative capacity and the ability to differentiate into multiple cell lineages. Within the normal BM and in pathological conditions, areas of hypoxia may have a role in maintaining stem cell fate or determining the fine equilibrium between their proliferation and differentiation. In this study, the transcriptional profiles, proliferation and differentiation potential of UCB CD133+ cells and BM mesenchymal cells (BMMC) exposed to normoxia and hypoxia were analysed and compared. Both progenitor cell populations responded to hypoxic stimuli by stabilising the HIF1-α protein. Short exposures to hypoxia increased the clonogenic myeloid capacity of UCB CD133+ cells and resulted in a significant increase in BMMC number. The differentiation potential of BMMC and UCB CD133+ cells was unaltered by hypoxia with the lineages tested. When their transcriptional profiles were compared, 183 genes in UCB CD133+ cells and 45 genes in BMMC were differentially regulated by hypoxia. These genes included known hypoxia-responsive targets such as BNIP3, PGK1, ENO2 and VEGF, and other genes not previously described to be regulated by hypoxia. Several of these genes, namely CDTSPL, CCL20, LSP1,NEDD9, TMEM45A, EDG-1 and EPHA3 were confirmed to be regulated by hypoxia using quantitative RT-PCR. These results therefore provide a global view of the signalling and regulatory network that controls oxygen sensing in human adult stem/progenitor cells derived from haematopoietic tissues.