Journal
NATURE
Volume 528, Issue 7581, Pages 212-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature16170
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Funding
- National Institute on Aging [R01 AG028127]
- National Institute on General Medical Sciences [R01 GM100196]
- Glenn Foundation for Medical Research postdoctoral fellowship
- National Institutes of Health (NIH) [S10OD010414]
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Somatic stem cells maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here we identify Ca2+ signalling as a central regulator of intestinal stem cell (ISC) activity in Drosophila. We show that dietary l-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response, and for an associated modulation of cytosolic Ca2+ oscillations that results in sustained high cytosolic Ca2+ concentrations. High cytosolic Ca2+ concentrations induce ISC proliferation by regulating Calcineurin and CREB-regulated transcriptional co-activator (Crtc). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca2+ oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca2+ levels allows effective integration of diverse mitogenic signals in ISCs to adapt their proliferative activity to the needs of the tissue.
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