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 Drosophila 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.
Subject(s)
Drosophila Proteins , Animals , Drosophila Proteins/metabolism , Hematopoietic Stem Cells/metabolism , Calcium Signaling , Hedgehog Proteins/metabolism , Drosophila/metabolism , Cell Differentiation , Gap Junctions/metabolism , Homeostasis , Stem Cell Niche , Hematopoiesis/physiologyABSTRACT
Stem cell homeostasis requires coordinated fate decisions among stem cells that are often widely distributed within a tissue at varying distances from their stem cell niche. This requires a mechanism to ensure robust fate decisions within a population of stem cells. Here, we show that, in the Drosophila hematopoietic organ, the lymph gland (LG), gap junctions form a network that coordinates fate decisions between blood progenitors. Using live imaging of calcium signaling in intact LGs, we find that blood progenitors are connected through a signaling network. Blocking gap junction function disrupts this network, alters the pattern of encoded calcium signals, and leads to loss of progenitors and precocious blood cell differentiation. Ectopic and uniform activation of the calcium-signaling mediator CaMKII restores progenitor homeostasis when gap junctions are disrupted. Overall, these data show that gap junctions equilibrate cell signals between blood progenitors to coordinate fate decisions and maintain hematopoietic homeostasis.