Project description: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. 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.
Project description: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.
Project description:Comparison of temporal gene expression profiles from Danio rerio skin. The RNA-seq data comprise 3 age groups at 5, 24 and 30 months. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Sperm cryopreservation is widely used in zebrafish conservation, but its long-term impacts on offspring impacts remains unclear. This study aims to evaluate whether cryopreservation of zebrafish sperm affects the metabolism of adult offspring. Adult zebrafish generated from cryopreserved sperm are compared to those from fresh sperm. Liver samples are subjected to sequencingto assess changes in potential functional pathways. The results will provide insights into the long-term impact of gamete cryopreservation on offspring metabolism.
Project description:Comparison of temporal small RNA gene expression profiles from Danio rerio brain. The smallRNA-seq data comprise 5 age groups at 6, 12, 24, 36 and 42 months. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of temporal small RNA gene expression profiles from Danio rerio skin. The smallRNA-seq data comprise 5 age groups at 6, 12, 24, 36 and 42 months. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)