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

Proc Natl Acad Sci U S A. 2023 Nov 7;120(45):e2303018120. doi: 10.1073/pnas.2303018120. Epub 2023 Oct 30.

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.

Keywords: Drosophila; calcium signaling; gap junctions; hematopoiesis; stem cell niche.

MeSH terms

  • Animals
  • Calcium Signaling
  • Cell Differentiation
  • Drosophila / metabolism
  • Drosophila Proteins* / metabolism
  • Gap Junctions / metabolism
  • Hedgehog Proteins / metabolism
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / metabolism
  • Homeostasis
  • Stem Cell Niche

Substances

  • Drosophila Proteins
  • Hedgehog Proteins