The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen.
An interferon-related signature in the transcriptional core response of human macrophages to Mycobacterium tuberculosis infection.
Cell line
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 SamplesThis 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 SamplesInterferon- (IFN-) or interleukin-4 (IL-4) prime macrophages towards classical (M1) or alternative (M2) activation, respectively. How IFN- and IL-4 prime epigenetic responses by altering expression of histone modifying enzymes and how this affects M1/M2 polarization is incompletely understood.
No associated publication
Specimen part, Treatment
View SamplesWe have used Affymetrix microarray-driven gene profiling to comprehensively describe the expression of mRNAs in the brainstem and hypothalamus in the adult male spontaneously hypertensive rat (SHR) as compared to its normotensive parental Wistar-Kyoto (WKY) strain.
No associated publication
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 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Off-pump coronary artery bypass surgery is associated with fewer gene expression changes in the human myocardium in comparison with on-pump surgery.
No sample metadata fields
View SamplesWe here report transcriptome profiles of human embryos at six successive developmental stages (i.e., Carnegie Stages 9 to 14), representing the first comprehensive gene expression database of early human organogenesis.
Transcriptome analysis of early organogenesis in human embryos.
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 Samples