Metabolism is an important regulatory entity controlling stem cell fate and fitness. In this project, we investigate the role of Glucose uptake on hematopoietic stem cell (HSC) function. We used the fluorescent glucose analog 2-NBDG to generate subgroups of HSCs with low, intermediate and high Glucose uptake. We observed a clear loss of stem cell potential in the high and to a lower extent in the intermediate HSC group. Now we work on unraveling the secrets of how Glucose uptake is influencing stem cell function, if potential can be conserved by changing Glucose uptake and last but not least we will analyze if there are changes upon aging and if so in which magnitude.
The function of HSCs can be altered by extrinsic signals such as cytokines and oxygen levels. We are exploring the relationship between ex vivo changes in pH and HSC function and metabolic status in both young and aged HSCs. The methods developed in this study could be used to improve culture conditions for ex vivo gene therapy treatments prior to stem cell transplantation and potentially rejuvenate aged HSC function.