Deregulated accumulation of myofibroblasts (MF) is central to liver fibrosis pathogenesis, but the mechanisms controlling myofibroblast fate remain poorly understood. Here we investigated whether Hedgehog (Hh) signaling regulates MF fate by modulating MF metabolism.
Hedgehog controls hepatic stellate cell fate by regulating metabolism.
Specimen part
View SamplesVanin1, a regulator of vitamin B5 metabolism, is expressed by sarcoma tumors. We evaluated its impact on sarcoma growth by using sarcoma cell lines derived from p16p19Vnn1-deficient mice and further transduced with an oncogenic RasV12 oncogene (R tumors) in the presence or not of a catalytically active (VR tumors) or mutated (VdR tumors) Vnn1 isoform.
Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity.
Specimen part, Cell line
View SamplesSympathetic neurons of SCG (Superior Cervical Ganglia) send axonal projections either along the external carotid arteries to innervate the salivary glands, or along the internal carotid arteries to the lacrimal and pineal glands, the eye, blood vessels and skin of the head, and the mucosa of the oral and nasal cavities. Previous studies using Wnt1Cre and R26R have defined the neural crest and mesodermal origins of vascular smooth muscle in the heart outflow tract and great vessels, although not specifically of the segments that are relevant for the projections of the SCG neurons. The third pharyngeal arch arteries are lined by neural crest-derived smooth muscle, and consequently, their derivatives, including the entirety of the external carotid arteries and only the base of the internal carotid arteries, also have a neural crest origin. In contrast, the dorsal aortae are lined by smooth muscle that is mesodermal in origin, and as a result, the internal carotid arteries from just above their origination from the common carotid arteries have a mesoderm-derived smooth muscle layer. To address the possibility that guidance cues for SCG neurons are selectively expressed by the external carotid vs. the internal carotid arteries, we isolated these segments of the vasculature from mouse embryos at E13.5 and extracted RNA to screen microarrays for differentially expressed genes.
Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons.
No sample metadata fields
View SamplesRecent studies have revealed a myriad of non-coding transcripts in different organisms. For instances, the presence of short bidirectional transcripts is a hallmark of active promoters in mammals, while upstream non-coding transcripts can be detected at most expressed genes in conditions where the RNA degradation machinery is inhibited. Here, we used RNA-seq with very high sequencing depth to characterize strand specific transcripts from primary mouse tissues. We found that a substantial fraction of gene promoters sustain expression of long non-coding antisense transcripts. These transcripts have an average size of 6 kb, have features of mature transcripts, but remain associated with the chromatin. We named this new class of non-coding RNAs Long Upstream Antisense Transcripts (LUAT). Strikingly, the LUAT and coding gene pairs are usually co-regulated, with the associated genes often/generally coding for transcriptional regulators functioning during development and cell differentiation. Indeed, these bidirectional promoters share several characteristic of developmental gene promoters, including large CpG islands and high degree of conservation, and display symetrical GC skews. Finally, we found that bidirectional promoters have enlarged platforms of Pol II initiation, associated with an intensified rate of early transcriptional elongation. We concluded that promoters of developmental regulators are characterized by a specialized mechanism of Pol II transcription, whereby Pol II poising is directly coupled to relaxed bidirectional transcription. Overall design: Expression of noncoding RNA transcripts in CD4-,CD8- double negative thymocytes from Rag2-/- mice was studied by strand-specific, ribosomal-depleted RNA-seq experiment, using Illumina sequencer
Divergent transcription is associated with promoters of transcriptional regulators.
Specimen part, Cell line, Subject
View SamplesHuman umbilical cord Whartons jelly stem cells (WHJSC) are gaining attention as a possible clinical source of mesenchymal stem cells for use in cell therapy and tissue engineering due to their high accessibility, expansion potential and plasticity. However, the cell viability changes that are associated to sequential cell passage of these cells are not known. In this analysis, we have identified the gene expression changes that are associated to cell passage in WHJSC.
Evaluation of the cell viability of human Wharton's jelly stem cells for use in cell therapy.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesThe study outcome was to evaluate the effect of the time on normal colon mucosa samples and possibly select specific genes whose expression is time-related, that could be used as detectors of tissue degradation.
Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesThe study outcome was to evaluate the effect of the time on tumor samples and possibly select specific genes whose expression is time-related, that could be used as detectors of tissue degradation.
Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesCompare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Age, Specimen part
View SamplesX-chromosome inactivation (XCI) provides a dosage compensation mechanism where, in each female cell, one of the two X chromosomes is randomly silenced. However, some genes on the inactive X chromosome and outside the pseudoautosomal regions escape from XCI and are expressed from both alleles (escapees). We investigated XCI at single-cell resolution combining deep single cellRNA sequencing with whole-genome sequencing to examine allelic-specific expression in 935 primary fibroblast and 48 lymphoblastoid single cells from five female individuals. In this framework we integrated an original method to identify and exclude doublets of cells. In fibroblast cells, we have identified 55 genes as escapees including five novel escapee genes. Moreover, we observed that all genes exhibit a variable propensity to escape XCI in each cell and cell type and that each cell displays a distinct expression profile of the escapee genes. A metric, the Inactivation Score—defined as the mean of the allelic expression profiles of the escapees per cell—enables us to discover a heterogeneous and continuous degree of cellular XCI with extremes represented by “inactive” cells, i.e., cells exclusively expressing the escaping genes from the active X chromosome and “escaping” cells expressing the escapees from both alleles. We found that this effect is associated with cell-cycle phases and, independently, with the XIST expression level, which is higher in the quiescent phase (G0). Single-cell allele-specific expression is a powerful tool to identify novel escapees in different tissues and provide evidence of an unexpected cellular heterogeneity of XCI. Overall design: Single-cell RNA seq study on 935 human fibroblasts and 48 lymphoblastoid cells from 5 female individuals, in order to investigate the X chromosome nactivation mechanism on a single cell level and to identify escapee genes
Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance.
Specimen part, Subject
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