Non-autonomous cell redox-pairs dictate niche homeostasis in multi-lineage stem populations

Abstract

Reactive oxygen species (ROS), predominantly derived from mitochondrial respiratory complexes, have evolved as key molecules influencing cell fate decisions like maintenance and differentiation. These redox-dependent events are mainly considered to be cell intrinsic in nature, on contrary our observations indicate involvement of these oxygen-derived entities as intercellular communicating agents. In multi-lineage Drosophila germline, neighbouring Germline Stem Cells (GSCs) and Cystic Stem Cells (CySCs) maintain differential redox thresholds where CySCs by virtue of their higher redox-state regulate physiological ROS levels of germline. Disruption of the intercellular redox equilibrium between the two adjoining stem cell populations results in deregulated niche architecture and loss of GSCs, which was mainly attributed to loss of contact-based receptions and uncontrolled CySC proliferation due to ROS-mediated activation of self-renewing signals. Our observations hint towards the crucial role of intercellular redox gradients originating from somatic progenitors, CySCs in niche stability where they function not only as a source of their own maintenance cues but also serve as non-autonomous redox moderators of germline immortality. Our findings underscore the complexity of niche homeostasis and predicate the importance of intercellular redox communication in understanding stem cell microenvironments.