UCSF

I found that an increase in intracellular pH is required for the differentiation of both a Drosophila epithelial stem cell lineage and mouse embryonic stem cells. This is the first demonstration of a role for intracellular pH in the regulation of stem cell differentiation, and our discovery of its importance in two different types of stem cell lineages suggests that this function for intracellular pH may be broadly conserved. In the Drosophila epithelial stem cell lineage, my findings support a model in which increased intracellular pH promotes terminal differentiation to a “stalk cell” fate by attenuating Hedgehog signaling, possibly through post transcriptionally regulating Smoothened levels. Our study of embryonic stem cells reveal that increased intracellular pH is required for differentiation measured by a battery of several different assays. Collectively, these findings demonstrate that intracellular pH can fine tune the process of cell differentiation, which opens up a new direction for understanding how cell physiology can influence cellular signaling.