This SuperSeries is composed of the SubSeries listed below.
A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats.
Sex, Specimen part
View SamplesThe supraoptic nucleus (SON) of the hypothalamus is an important integrative brain structure that co-ordinates responses to perturbations in water balance and regulates maternal physiology through the release of the neuropeptide hormones vasopressin and oxytocin into the circulation. Both dehydration and lactation evoke a dramatic morphological remodelling of the SON, a process known as function-related plasticity. We hypothesise that some of the changes seen in SON remodelling are mediated by differential gene expression, and have thus used microarrays to document global changes in transcript abundance that accompany chronic dehydration in female rats, and in lactation. In situ hydridisation analysis has confirmed the differential expression of 3 of these genes, namely Tumour necrosis factor induced protein 6, Gonadotrophin inducible transcription factor 1 and Ornithine decarboxylase antizyme inhibitor 1. Comparison of differential gene expression patterns in male and female rats subjected to dehydration and in lactating rats has enabled the identification of common elements that are significantly enriched in gene classes with particular functions. Two of these are related to the requirement for increased protein synthesis and hormone delivery in the physiologically stimulated SON (translation initiation factor activity and endoplasmic reticulum-Golgi intermediate compartment respectively), whilst others are consistent with concept of SON morphological plasticity (collagen fibril organisation, extracellular matrix organization and biogenesis, extracellular structure organization and biogenesis and homophilic cell adhesion). We suggest that the genes co-ordinately regulated in the SON as a consequence of dehydration and lactation form a network that mediates the plastic processes operational in the physiologically activated SON.
Transcriptomic analysis of the osmotic and reproductive remodeling of the female rat supraoptic nucleus.
Sex, Specimen part, Treatment
View SamplesThe hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei are important integrative structures that regulate co-ordinated responses to perturbations in cardiovascular homeostasis. Through descending projections from parvocellular neurons to the brainstem, the PVN acts as an autonomic 'premotor nucleus', regulating reflex changes in sympathetic nerve activity that are involved in blood pressure and blood volume regulation. Endocrine responses are mediated through axonal projections from SON and PVN magnocellular neurons (MCNs) to the capillaries of the posterior pituitary neural lobe. In response to dehydration, a massive release of the antidiuretic peptide hormone vasopressin (VP) into the circulation is accompanied by a dramatic functional remodelling of the HNS. We have used microarrays to comprehensively catalogue the genes expressed in the PVN, the SON and the neurointermediate lobe (NIL) of the pituitary gland. Further, we have identified transcripts that are regulated as a consequence of dehydration, as well as RNAs that are enriched in either the PVN or the SON. We suggest that these differentially expressed genes represent candidate regulators and effectors of HNS activity and remodelling.
A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats.
Sex, Specimen part
View SamplesWe have addressed the question of how different rodent species cope with the life-threatening homeostatic challenge of dehydration at the level of transcriptome modulation in the supraoptic nucleus (SON), a specialised hypothalamic neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone arginine vasopressin (AVP). AVP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of AVP from SON axon terminals located in the posterior pituitary, and this is accompanied by a plethora of changes in the morphology, electrophysiological properties, biosynthetic and secretory activity of this structure. Microarray analysis was used to generate a definitive catalogue of the genes expressed in the mouse SON, and to describe how the gene expression profile changes in response to dehydration. Comparison of the genes differentially expressed in the mouse SON as a consequence of dehydration with those of the rat has revealed many similarities, pointing to common processes underlying the function-related plasticity in this nucleus. In addition we have identified many genes that are differentially expressed in a species-specific manner. However, in many cases, we have found that the hyperosmotic cue can induce species-specific alterations in the expression of different genes in the same pathway. The same functional end can be served by different means, via differential modulation, in different species, of different molecules in the same pathway. We suggest that pathways, rather than specific genes, should be the focus of integrative physiological studies based on transcriptome data.
Hypothalamic transcriptome plasticity in two rodent species reveals divergent differential gene expression but conserved pathways.
Sex, Specimen part
View SamplesIn these studies we have for the first time described the transcriptome of the rat SFO, and have in addition identified genes the expression of which is significantly modified by either water or food deprivation.
Microarray analysis of the transcriptome of the subfornical organ in the rat: regulation by fluid and food deprivation.
Sex, Specimen part
View SamplesWe have used microarrays to comprehensively describe the transcriptomes of the supraoptic nucleus (SON), the paraventricular nucleus (PVN) and the neurointermediate lobe (NIL) of adult male Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats, as well as the paraventricular nucleus of Wistar (WIST) rats. Comparison of these gene lists has enabled us to identify surprisingly large differences in hypothalamo-neurohypophyseal system gene expression patterns in these three strains. We have also shown that different transcript populations are enriched in the PVN and the SON of SD and WKY rats. The transcriptome differences catalogued here may be molecular substrates for the neuro-humoral phenotypic differences exhibited by different strains of rats.
The transcriptome of the rat hypothalamic-neurohypophyseal system is highly strain-dependent.
Sex, Specimen part
View SamplesTo understand the nature of glucocorticoids targeting non-immune cell function, we generate RNA sequencing data from 3 human podocyte cell lines derived from 3 kidney transplant donors and identify the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells.Our results represent a significant step forward in the genome-wide characterization of the molecular effects of glucocorticoids on human podocytes. The resource generated in this study is important for understanding the targeting of non-immune cell function by glucocorticoids and also for designing more specific podocyte-targeted agents for MCN therapy. Overall design: Transcriptome profiles of human podocytes treated with vehicle and dexamethasone were generated by RNA-sequencing using Illumina HiSeq 2500
RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways.
Specimen part, Subject
View SamplesThe area postrema (AP) is a sensory circumventricular organ characterised by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague Dawley (SD) and Wistar Kyoto (WKY) rat and present here a comprehensive catalogue of gene expression, focussing specifically on the population of ion channels, receptors and G protein-coupled receptors (GPCRs) expressed in this sensory tissue; of the GPCRs expressed in the rat AP we identified ~36% that are orphans having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72-hours dehydration (DSD) and 48-hours fasting (FSD) and have performed microarrays under these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat (SHR) AP compared to the normotensive WKY controls however. Finally, analysis of these hypertension-related elements revealed genes that are involved in both the regulation of blood pressure and immune function and as such are excellent targets for further study.
The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat.
Sex, Specimen part
View SamplesSalt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. Upon osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared to euhydrated (EU) controls in terms of drinking and eating behaviour, body weight and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL
A comparison of physiological and transcriptome responses to water deprivation and salt loading in the rat supraoptic nucleus.
Specimen part
View SamplesRetinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In the Pou4f3-Cre:Rb1 flox/flox (Rb1 cKO) inner ear, utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of Rb1 cKO cochlea and utricle.
Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs.
Age, Specimen part
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