Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo by James...

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

BloodVolume 121(13):2483-2493

March 28, 2013

©2013 by American Society of Hematology

Glucose enhances HSC formation in the zebrafish AGM region.

James M. Harris et al. Blood 2013;121:2483-2493


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).



The effect of glucose is dependent on uptake rather than insulin signaling.



Glucose levels influence HSC formation via increased energy metabolism.



ROS produced by mitochondrial activity cause HSC expansion.



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...



Downstream targets of hif1α are temporally regulated to modulate HSC induction to match nutrient availability.



Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo by James...

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