Maintenance of hematopoietic stem cell niche homeostasis requires gap junction-mediated calcium signaling.

Abstract

Regulation of stem cells requires coordination of the cells that make up the stem cell niche. Here, we describe a mechanism that allows communication between niche cells to coordinate their activity and shape the signaling environment surrounding resident stem cells. Using the <i>Drosophila</i> hematopoietic organ, the lymph gland, we show that cells of the hematopoietic niche, the posterior signaling center (PSC), communicate using gap junctions (GJs) and form a signaling network. This network allows PSC cells to exchange Ca²⁺ signals repetitively which regulate the hematopoietic niche. Disruption of Ca²⁺ signaling in the PSC or the GJ-mediated network connecting niche cells causes dysregulation of the PSC and blood progenitor differentiation. Analysis of PSC-derived cell signaling shows that the Hedgehog pathway acts downstream of GJ-mediated Ca²⁺ signaling to modulate the niche microenvironment. These data show that GJ-mediated communication between hematopoietic niche cells maintains their homeostasis and consequently controls blood progenitor behavior.