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GSE50570
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic Ductal Adenocarcinoma (PDA) is a critical health issue in cancer field with little new therapeutic options. Several evidences support an implication of intra-tumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within pathophysiology and clinical course of PDA, mainly through tumor recurrence and neuropathic pain, remains unknown neglecting a putative therapeutic window. Here, we report that intra-tumoral microenvironment is a mediator of PDA Associated Neural Remodeling (PANR). With laser capture microdissection of stromal/tumoral compartment from human PDA followed by cDNA based microarray analyses we highlighted numerous factors expressed by stromal compartment that could impact on neuroplastic changes; among them, the Slit2/Robo axon guidance pathway. Using co-culture in vitro, we showed that stromal secreted Slit2 increases DRG neurite outgrowth and Schwann cells migration/proliferation by modulating N-Cadherin/-Catenin signaling. Importantly, Slit2/Robo signaling inhibition disrupts this stromal/neural connection. Finally, we revealed in vivo that Slit2 expression is correlated with neural remodeling within Human and mouse PDA. These results demonstrate the implication of microenvironment, through secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of stromal/neural compartment dialogue by using Slit2/Robo pathway inhibitors for treatment of pancreatic cancer recurrence and associated pain.
Publication Title
Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD27 and CD45RA can be used to split T cells into 4 subsets, nave cells, CD27+CD45RA+, central memory cells CD27+CD45RA-, effector memory cells CD27-CD45RA-, effector memory CD45RA re-expressing cell, CD27-CD45RA+. It is with in this final EMRA subset that it is belived the senenscent T cells reside. Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP), to date a SASP has not been demonstrated in T cells.
Publication Title
Human CD8<sup>+</sup> EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces ER stress response as major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
Publication Title
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
Publication Title
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
Publication Title
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Analysis of gene expression profiles of epididymal fat from DIO rats
Publication Title
Assessment of diet-induced obese rats as an obesity model by comparative functional genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
It is well-established that neurons in the adult mammalian central nervous system are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX), retinal ganglion cells (RGC) regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after optic nerve crush can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration.
Publication Title
Time Course Analysis of Gene Expression Patterns in Zebrafish Eye During Optic Nerve Regeneration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinsons disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration.
Publication Title
Parkinson disease-associated DJ-1 is required for the expression of the glial cell line-derived neurotrophic factor receptor RET in human neuroblastoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 335 Downloadable Samples
NextSeq 500
Description
Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. The principal neural unit in the bowel encoding these stimuli is the visceral sensory neuron with endings at the mucosa, intramurally and along mesenteric blood vessels. Sensory neurons activate reflex pathways and give rise to conscious sensation, however, the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by the current paucity of molecular markers. Here we overcome these limitations by comprehensive transcriptomic profiling and unsupervised clustering of single colonic sensory neurons revealing 7 classes characterised from both lumbar splanchnic (LSN) and pelvic nerves (PN). We identify and classify neurons based on novel marker genes, confirm translation of patterning to protein expression and show subtype-selective differential agonist activation, describing sensory diversity encompassing all modalities of colonic neuronal sensitivity. Overall design: Sensory neurons innervating the mouse colorectum were labelled by retrograde tracer injection. Single-cell RNAseq was performed on 399 dissociated colonic sensory neurons isolated from thoracolumbar (T10-L1) and lumbosacral (L5-S2) dorsal root ganglia distributed over six 96-well plates. 13 additional negative controls were collected.
Publication Title
Single-cell RNAseq reveals seven classes of colonic sensory neuron.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples