A gap-junction-mediated, calcium-signaling network controls blood progenitor fate decisions in hematopoiesis

• Published in: Current biology Vol. 31; no. 21; pp. 4697 - 4712.e6
• Main Authors: Ho, Kevin Y.L., Khadilkar, Rohan J., Carr, Rosalyn L., Tanentzapf, Guy
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 08.11.2021
• Subjects: Animals; Calcium; Calcium Signaling; Cell Differentiation - physiology; cell-cell communication; cellular signaling; Drosophila; Drosophila - physiology; Drosophila Proteins - metabolism; gap junctions; Gap Junctions - metabolism; hematopoiesis; Hematopoiesis - physiology; lymph gland; prohemocytes; gap junctions; hematopoiesis; lymph gland; Drosophila; calcium signaling; cellular signaling; prohemocytes; cell-cell communication
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2021.08.027

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. [Display omitted] •Drosophila blood progenitors use gap junctions to form a multicellular network•The gap-junction-mediated network helps blood progenitors coordinate fate decisions•Ca+2 signaling in blood progenitors is regulated by the gap junction-mediated network•Ca+2 signaling downstream of gap junctions regulates blood progenitor fate decisions Ho et al. show that, during Drosophila hematopoiesis, gap junctions link blood progenitors in a multicellular calcium-signaling network that ensures coordination of fate decisions. Gap junctions equilibrate calcium signaling between blood progenitors, which ensures collective cell behavior among hundreds of progenitors in the hematopoietic organ.