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GSE8696
Caenorhabditis elegans
9 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Hemes are essential but potentially cytotoxic cofactors that participate in critical and diverse biological processes. Although the pathway and intermediates for heme biosynthesis have been well defined, the intracellular networks which mediate heme trafficking remain unknown. Caenorhabditis elegans and related helminths are natural heme auxotrophs requiring environmental heme for growth and development. We exploited this auxotrophy to identify HRG-1 and HRG-4 in C. elegans and show that they are essential for heme homeostasis and normal vertebrate development. We demonstrate that heme deficiency upregulates expression of hrg-4 and its evolutionarily conserved paralog hrg-1. Depletion of either HRG-1 or HRG-4 in worms results in disruption of organismal heme sensing and abnormal response to heme analogs. HRG-1 and HRG-4 are novel transmembrane proteins that bind heme and have evolutionarily conserved functions. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations, and, most strikingly, profound defects in erythropoiesis - phenotypes that are fully rescued by worm HRG-1. These findings reveal unanticipated and conserved pathways for cellular heme trafficking in animals that defines the paradigm for eukaryotic heme transport. Uncovering the mechanisms of heme transport in C. elegans will provide novel insights into human disorders of heme metabolism and generate unique anthelmintics to combat worm infestations.
Publication Title
Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
We performed RNA sequencing analysis of hepatic gene expression a few hours after amlexanox treatment, and identified over 1700 differentially expressed genes. Pathway analysis of these differentially regulated genes revealed that the top two most enriched pathways were the adipocytokine signaling pathway and the Jak-STAT signaling pathway. Overall design: RNA-seq analysis of hepatic gene expression was used to identify differentially expressed genes in response to Amlexanox treatment.
Publication Title
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response.
Sample Metadata Fields
Specimen part, Time
View Samples