Regulation of blood cell transdifferentiation by oxygen sensing neurons

Transdifferentiation generates specialized cell types independent of stem or progenitor cells. Despite the unique process, it remains poorly understood how transdifferentiation is regulated in vivo. Here we reveal a mechanism of environmental control of blood cell transdifferentiation in a Drosophila model of hematopoiesis. Functional lineage tracing provides evidence for transdifferentiation from macrophage-like plasmatocytes to crystal cells that execute melanization. Interestingly, this transdifferentiation is promoted by neuronal activity of a specific subset of sensory neurons, in the caudal sensory cones of the larva. Crystal cells develop from plasmatocyte clusters surrounding the sensory cones, triggered by environmental conditions: oxygen sensing, and the atypical guanylyl cyclase Gyc88E specifically expressed in the sensory cone neurons, drive plasmatocyte-to-crystal cell transdifferentiation. Our findings reveal an unexpected functional and molecular link of environment-monitoring sensory neurons that govern blood cell transdifferentiation in vivo, suggesting similar principles in vertebrate systems where environmental sensors and blood cell populations coincide.