2/28/2024 0 Comments Stem cell differenciation![]() ![]() ![]() “They lay very few eggs, suggesting that there must be defects in oogenesis.” “ DheN2-null flies are almost infertile,” Nystul says. Nystul and colleagues, led by graduate student Bryne Ulmschneider, worked with Barber’s group to analyze Drosophila lacking DNhe2, a Na +–H + exchanger that increases pHi by transporting protons out of the cell. “pH dynamics may therefore be a more common component of cellular differentiation than we previously thought.” “I’m always interested in new ways for cells to control differentiation,” Nystul explains. In fact, Diane Barber and colleagues at the University of California, San Francisco (UCSF) view protonation as a reversible posttranslational modification akin to phosphorylation or ubiquitination ( 4).īarber and colleagues have been studying the effects of pHi in tissue culture cells, but a fellow group leader at UCSF, Todd Nystul, wondered whether pHi might regulate the differentiation of stem cells in vivo. By altering the protonation and charge of amino acids such as histidine, changes in pHi can affect protein conformation and activity. Though this protects cells from the damaging effects of acids and alkalis, it is now known that small changes in intracellular pH (pHi) can also act as cytosolic signals that regulate a variety of processes, from cell cycle progression ( 2) to membrane trafficking ( 3). ULMSCHNEIDER PHOTO COURTESY OF THI NGUYEN NYSTUL PHOTO COURTESY OF THE AUTHORĬells use homeostatic mechanisms to maintain their cytoplasm at a pH close to neutral. An increase in pHi also promotes the differentiation of mouse embryonic stem cells, suggesting that pH dynamics may be a common regulatory mechanism in a variety of stem cell populations. This increase in pHi is smaller, and overall pH is lower, upon knockdown of the Na +–H + exchanger DNhe2, resulting in impaired follicle cell maturation and oogenesis defects, at least in part because of a failure to down-regulate Hedgehog signaling at the appropriate stage of differentiation. A fluorescent pH biosensor shows that, in wild-type Drosophila (right), the pHi of follicle stem cells at the anterior end of the follicle epithelium increases as the cells differentiate to mature follicle cells in more posterior positions. FOCAL POINT Bryne Ulmschneider (left), Todd Nystul (center), and colleagues reveal that an increase in intracellular pH (pHi) promotes the differentiation of two different types of stem cells.
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