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Kinetics of blood cell differentiation during hematopoiesis revealed by quantitative long-term live imaging


Authors:
Kevin Ho 1; Rosalyn Carr 2; Alexandra Dvoskin 1; Guy Tanentzapf 1

Affiliations:
1) Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada, V6T 1Z3; 2) School of Biomedical Engineering, University of British Columbia, Vancouver, Canada, V6T 1Z3

Keywords:
e. hematopoietic stem cells; n. live imaging

Stem cells typically reside in a specialized physical and biochemical environment that facilitates regulation of their behavior. For this reason, stem cells are ideally studied in contexts that maintain this precisely constructed microenvironment while still allowing for live imaging. Here, we describe a long-term organ culture and imaging strategy for hematopoiesis in flies that takes advantage of powerful genetic and transgenic tools available in this system. We find that fly blood progenitors undergo self-renewal, suggesting that they are true stem cells. Using quantitative imaging to simultaneously track markers for stemness and differentiation in progenitors, we identify two types of differentiation that exhibit distinct kinetics. Moreover, we find that infection-induced activation of hematopoiesis occurs through modulation of the kinetics of cell differentiation. Overall, our results show that even subtle shifts in proliferation and differentiation kinetics can have large, aggregate effects to transform stem cells from a quiescent to an activated state.