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Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo by James M. Harris, Virginie Esain, Gregory M. Frechette, Lauren.

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Presentation on theme: "Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo by James M. Harris, Virginie Esain, Gregory M. Frechette, Lauren."— Presentation transcript:

1 Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo by James M. Harris, Virginie Esain, Gregory M. Frechette, Lauren J. Harris, Andrew G. Cox, Mauricio Cortes, Maija K. Garnaas, Kelli J. Carroll, Claire C. Cutting, Tahsin Khan, Philip M. Elks, Stephen A. Renshaw, Bryan C. Dickinson, Christopher J. Chang, Michael P. Murphy, Barry H. Paw, Matthew G. Vander Heiden, Wolfram Goessling, and Trista E. North Blood Volume 121(13):2483-2493 March 28, 2013 ©2013 by American Society of Hematology

2 Glucose enhances HSC formation in the zebrafish AGM region. James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

3 Glucose accelerates the onset and output of definitive hematopoiesis in the AGM. (A) Time- course analysis by in situ hybridization for runx1 in 3-hour intervals from 18 to 36 hpf revealed earlier and enhanced expression after glucose exposure (n ≥ 35/tx). James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

4 The effect of glucose is dependent on uptake rather than insulin signaling. James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

5 Glucose levels influence HSC formation via increased energy metabolism. James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

6 ROS produced by mitochondrial activity cause HSC expansion. James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

7 Hif1α activity induced by elevated ROS mediates the effect of glucose metabolism on HSCs. (A) Exposure to CoCl2 (500μM) or the hif1α prolyl hydroxylase inhibitor DMOG (500μM) expanded runx1/cmyb expression and rescued the impairment of HSC formation induced... James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

8 Downstream targets of hif1α are temporally regulated to modulate HSC induction to match nutrient availability. James M. Harris et al. Blood 2013;121:2483-2493 ©2013 by American Society of Hematology

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