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Signal integration by Ca(2+) regulates intestinal stem-cell activity.

Hansong Deng1, Akos A Gerencser1, Heinrich Jasper1

  • 1The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.

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|December 4, 2015
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Summary

Dietary L-glutamate boosts intestinal stem cell (ISC) division and gut growth in Drosophila. Calcium (Ca2+) signaling, regulated by metabotropic glutamate receptors (mGluRs), controls ISC proliferation via Calcineurin and Crtc.

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Area of Science:

  • Stem cell biology
  • Calcium signaling
  • Drosophila melanogaster model organism

Background:

  • Somatic stem cells maintain tissue homeostasis through dynamic proliferation and differentiation.
  • Stress and metabolic cues influence stem cell behavior.
  • Intestinal stem cells (ISCs) are crucial for gut health and regeneration.

Purpose of the Study:

  • To identify key regulators of intestinal stem cell (ISC) activity in Drosophila.
  • To elucidate the role of calcium (Ca2+) signaling in ISC proliferation.
  • To understand how dietary cues modulate ISC behavior.

Main Methods:

  • Investigated Drosophila melanogaster as a model system.
  • Utilized dietary L-glutamate as a stimulus.
  • Examined the role of metabotropic glutamate receptors (mGluRs) in ISCs.
  • Measured cytosolic Ca2+ oscillations and concentrations.
  • Analyzed the involvement of Calcineurin and CREB-regulated transcriptional co-activator (Crtc).

Main Results:

  • Dietary L-glutamate stimulates ISC division and gut growth.
  • Metabotropic glutamate receptors (mGluRs) are essential for this response in ISCs.
  • mGluR activation modulates cytosolic Ca2+ oscillations, leading to sustained high Ca2+ levels.
  • High cytosolic Ca2+ induces ISC proliferation through Calcineurin and Crtc.
  • ISCs exhibit reversible transitions between Ca2+ oscillation states, reflecting proliferation modes.

Conclusions:

  • Calcium (Ca2+) signaling is a central regulator of intestinal stem cell (ISC) activity in Drosophila.
  • Dynamic regulation of intracellular Ca2+ allows ISCs to integrate diverse signals and adapt proliferation.
  • This mechanism enables ISCs to adjust proliferative activity according to tissue needs in response to dietary and stress stimuli.