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This study demonstrates that neural stem cells (NSCs) in Drosophila actively regulate intracellular calcium levels to maintain their identity and control cell fate decisions. Proliferating neuroblasts maintain low cytosolic calcium, while differentiated daughter cells show elevated levels, and artificially raising calcium in stem cells slows proliferation and promotes differentiation. The research further shows that calcium stored in the endoplasmic reticulum, maintained by the pump SERCA, is required for proper Notch signaling, a core pathway governing stem cell behavior, and that disrupting this calcium store reprograms one type of neuroblast into another.
Why it matters
Understanding how calcium dynamics regulate stem cell identity and fate transitions has potential relevance for developmental disorders and brain cancers, particularly tumors arising from neural stem cells that have lost normal proliferative controls. These findings could inform future therapeutic strategies targeting calcium regulatory pathways in stem cell-related diseases.
⚠️ Preprint – Noch nicht peer-reviewed
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Asymmetrically dividing neural stem cells (NSCs) provide the foundation for brain development by coupling self-renewal to the generation of diverse differentiated progeny. Yet how NSCs actively sculpt intracellular Ca2+ dynamics to drive developmental programs and cell behaviors across fate transitions remains poorly understood. Here we identify a role for intracellular Ca2+ set points in maintaining NSC identity and function in asymmetrically dividing Drosophila neuroblasts (NB). We find that proliferative NBs maintain low baseline cytosolic Ca2+, whereas differentiated progeny exhibit elevated cytosolic Ca2+. Experimentally increasing cytosolic Ca2+ slows proliferation and promotes differentiation. We further identify specific Ca2+ regulatory factors that are required for proliferation. Endoplasmic Reticulum (ER) luminal Ca2+ also differs by cell fate and depletion of ER Ca2+ in type II NB by loss of SERCA (Sarcoendoplasmic Reticulum ATPase) is sufficient to reprogram type II NB into a type I-like NB fate. Mechanistically, SERCA-dependent ER luminal Ca2+ is required for Notch receptor processing, trafficking and activation in NBs linking organellar Ca2+ to a core stem cell signaling pathway. Thus, NSCs and their progeny actively and distinctly shape intracellular Ca2+ landscapes to drive developmental programs and cell behaviors, with implications for developmental disorders and cancer.
Source: Neural stem cells shape intracellular calcium landscapes to control cell identity and function