Elucidating the role of mitochondrial dynamics and endosomal protein sorting in Drosophila blood cell homeostasis

Abstract

Blood cell homeostasis depends on the co-ordination of various intracellular and extracellular cues. Sub-cellular organelles play critical roles in post-transcriptional control of signal generation and attenuation. Recently endosomal and mitochondrial proteins have been shown to play active roles in maintaining stem and progenitor cell homeostasis in mouse and Drosophila. We aim to understand the role of organelles in progenitor maintenance and cell fate determination in Drosophila hematopoiesis. Previous studies showed that Asrij/OCIAD1 localizes to endosomes and mitochondria and can maintain stemness in Drosophila and mouse hematopoiesis. This thesis contributed to identifying critical immune pathways regulated by Asrij and validated candidates from a previous study of the asrij mutant hematopoietic proteome.Further using the Drosophila genetics and the lymph gland as a model of hematopoiesis, here I explore the role of mitochondria and endosomes in progenitor maintenance and differentiation by imaging-based in situ analyses. My studies reveal that the mitochondrial dynamics regulators and the Endosomal Sorting Complex Required for Transport (ESCRT) actively control blood progenitor heterogeneity, homeostasis, and lineage choice.