Clinical Significance: Understanding the differences in colorectal cancer (CRC) aggressiveness and clinical outcomes in relation to tumor stage and different molecular subsets is at most important for designing treatment regimens. However, molecular signatures for specific phenotypic subsets that predict the aggressiveness and clinical outcomes of CRC, specifically in advanced disease stage are lacking. Therefore, for the first time, the current study has identified a set of molecular markers that are associated with aggressive Stage III CRCs that exhibited microsatellite stable and mutant p53 phenotypic features. These findings might aid in designing aggressive treatment regimens and help to provide insights into the development of novel therapeutic targets.
Prognostic significance and gene expression profiles of p53 mutations in microsatellite-stable stage III colorectal adenocarcinomas.
Specimen part, Disease, Disease stage
View SamplesCD27 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.
Human CD8<sup>+</sup> EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK.
Sex
View SamplesAnkrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.
Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.
Specimen part
View SamplesThe purpose of this study was to define biomarkers of sensitivty and mechanisms of resistance to the KDM1A/LSD1 inhibtor SP-2509 (HCI-2509) in Ewing sarcoma cell lines. We report that regardless of drug sensitivity all cell lines engage the UPR and ER-stress response following treatment with SP-2509 resulting in apoptotic cytotoxicity. In addition hypersentsitive cell lines shared a common basal transcriptnomic profile, with hypersensitive cell lines signficantly inducing ETS1 which was not observed in sensitive cell lines. Overall design: 6 Ewing sarcoma cell lines were treated with either vehicle control (DMSO) or the reversible LSD1/KDM1A inhibitor SP-2509 (2uM) for 48hrs. Three SP-2509 hypersensitive (IC50< 300nM)(A673, TC32, TC252) and three SP-2509 sensitive (IC50>900nM) (EWS-502, ES-2 and TC71) cell lines were investigated. Paired RNA from three indpendent experiments per cell line was analyzed.
Therapeutic Targeting of KDM1A/LSD1 in Ewing Sarcoma with SP-2509 Engages the Endoplasmic Reticulum Stress Response.
Treatment, Subject
View SamplesAnalysis of gene expression profiles of epididymal fat from DIO rats
Assessment of diet-induced obese rats as an obesity model by comparative functional genomics.
No sample metadata fields
View SamplesThis study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a (10uM and/or 50uM) for 48 hours.
Nutlin-3a efficacy in sarcoma predicted by transcriptomic and epigenetic profiling.
No sample metadata fields
View SamplesHere we show that the histone methyltransferase MLL4 (Kmt2d) is required for stem cell activity and an aggressive form of acute myeloid leukemia (AML) harboring the MLL-AF9 oncogene. MLL4 exerts its function by regulating transcriptional programs associated with the anti-oxidant response. Overall design: The role of Mll4 (Kmt2d) in regulating the transcriptome of primary and transformed hematopoietic stem cells was studied.
DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.
No sample metadata fields
View SamplesIntegration 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.
Single-cell RNAseq reveals seven classes of colonic sensory neuron.
Specimen part, Cell line, Subject
View SamplesBackground and objective: The chromosome 13 deletion (del(13)) represents one of the most frequent chromosomal alterations in multiple myeloma (MM). del(13) is associated with an unfavorable prognosis, although there is an increasing agreement that its prognostic relevance has to be related to the ploidy status and the presence of different chromosomal translocations. This study is aimed at providing a comprehensive analysis of the transcriptional features of del(13) in MM. Design and methods: Highly purified plasma cells from 80 newly diagnosed MM patients were characterized by means of FISH and high-density oligonucleotide microarray for gene expression profiling and chromosomal alterations. Results: We identified 67 differentially expressed genes in the del(13)+ and del(13)- groups, all of which downregulated in the del(13)+ cases: 44 mapped along the whole chromosome 13, seven on chromosome 11 and three on chromosome 19. Functional analyses of the selected genes indicated their involvement in protein biosynthesis, ubiquitination and transcriptional regulation. An integrative genomic approach based on regional analyses of the gene expression data identified distinct chromosomal regions whose global expression modulation could differentiate del(13)+, in particular the upregulation of 1q21-1q42 and the downregulation of 19p and almost the entire chromosome 11. FISH analyses confirmed the close relationship between del(13)+ and the presence of extracopies of 1q21-1q42 (P=6x10-4) or the absence of chromosome 11 and 19 trisomy (P=5x10-4). Interpretation and conclusions: Our results indicate that distinct types of chromosomal aberrations are closely related to the transcriptional profiles of del(13)+, suggesting that the contribution of del(13) on the malignancy should be considered together with associated abnormalities.
Integrative genomic analysis reveals distinct transcriptional and genetic features associated with chromosome 13 deletion in multiple myeloma.
Sex
View SamplesThis GEO submission includes RNAseq raw data (fastq) and processed data (using ASpli 1.6.0) from samples obtained in the wild type and the single prefoldin4 and lsm8 mutants in three different environmental conditions as well as in the triple prefoldin2 prefoldin4 prefoldin6 mutant growth in standard conditions. Overall design: 28 biological samples from 10 different conditions and genopypes, including the Col-0 WT in each condition (standard, cold and salt conditions)
Prefoldins contribute to maintaining the levels of the spliceosome LSM2-8 complex through Hsp90 in Arabidopsis.
Specimen part, Subject
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