Blood stem cells with low levels of Sca-1 differentiated into red blood cell progenitors seven times more often than cells high in Sca-1 when exposed to erythropoietin, a growth factor that promotes red blood cell production. Conversely, when stem cells were exposed to granulocytemacrophage colony-stimulating factor, which stimulates white blood cell formation, those that were highest in Sca-1 were the most likely to become white cells. Yet, in both experiments, all three groups of cells retained characteristics of stem cells.
Huang and Chang then looked at the proteins GATA1 and PU.1, transcription factors that normally favor differentiation into red and white blood cells, respectively. Blood stem cells that were low in Sca-1 (and most prone to become red blood cells) had much more GATA1 than did the high- and medium-Sca-1 cells. Stem cells high in Sca-1 (and least prone to become red blood cells) had the highest levels of PU.1.
But most important, the differences in Sca-1, GATA1 and PU.1 levels across the three cell groups became less pronounced over time, as did the variability in the cells propensity to differentiate, suggesting that the differences are transient.
In a final step, Huang and Chang used microarrays to look at the cells entire genome. Again, they found tremendous variability within the apparently uniform cell population: more than 3,900 genes were differentially expressed (turned on or off) between the low- and high-Sca-1 cells. And again, this variability was dynamic: the differences diminished over time, with gene activity in both the low- and high-Sca-1 cells becoming more like that in the middle group.
Together, the findings make the case that a slow fluctuation or cycling of gene activity tends to maintain cells in a stable state, while also priming them to differentiate wh
|Contact: Bess Andrews|
Children's Hospital Boston