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Series GSE43186 Query DataSets for GSE43186
Status Public on Feb 15, 2013
Title Glucose Metabolism impacts the spatio-temporal onset and magnitude of HSC induction in vivo
Organism Danio rerio
Experiment type Expression profiling by array
Summary Many pathways regulating blood formation have been elucidated, yet how each coordinates with embryonic biophysiology to modulate the spatio-temporal production of hematopoietic stem cells (HSCs) is currently unresolved. Here, we report that glucose metabolism impacts the onset and magnitude of HSC induction in vivo. In zebrafish, transient elevations in physiological glucose levels elicited dose-dependent effects on HSC development, including enhanced runx1 expression and hematopoietic cluster formation in the Aorta-Gonad-Mesonephros (AGM) region; embryonic-to-adult transplantation studies confirmed glucose increased functional HSCs. Glucose uptake was required to mediate the enhancement in HSC development; likewise, metabolic inhibitors diminished nascent HSC production and reversed glucose-mediated effects on HSCs. Increased glucose metabolism preferentially impacted hematopoietic and vascular targets, as determined by gene expression analysis, through mitochondrial-derived reactive oxygen species (ROS)-mediated stimulation of hypoxia inducible factor 1α (hif1α); epistasis assays demonstrated hif1α regulates HSC formation in vivo and mediates the dose-dependent effects of glucose metabolism on the timing and magnitude of HSC production. We propose this fundamental metabolic-sensing mechanism enables the embryo to respond to changes in environmental energy input and adjust hematopoietic output to maintain embryonic growth and ensure viability.
Overall design We performed microarray analysis to explore the changes in gene expression that occur in repsonse to altered metabolism during the induction of developmental hematopoeisis. We compared RNA from zebrafish raised in a solution of 1% glucose from 12-36hpf vs controls. Two biological replicates for each condition were performed.
Contributor(s) Harris JM, Esain V, Freschette GM, Harris LJ, Cox AG, Cortes M, Garnaas MK, Carroll KJ, Cutting CC, Khan Y, Elks PM, Renshaw SA, Dickinson BC, Chang CJ, Murphy MP, Paw BH, Vander Heiden MG, Goessling W, North TE
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Submission date Dec 28, 2012
Last update date Jan 25, 2018
Contact name Trista North
Organization name BIDMC
Street address 3 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL1319 [Zebrafish] Affymetrix Zebrafish Genome Array
Samples (4)
GSM1058032 whole zebrafish 36hpf, control, biological replicate 1
GSM1058033 whole zebrafish 36hpf, control, biological replicate 2
GSM1058034 whole zebrafish 36hpf, glucose treated, biological replicate 1
BioProject PRJNA184860

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Supplementary file Size Download File type/resource
GSE43186_RAW.tar 7.5 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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