We showed that a large number of genes and exons were deregulated in colorectal adenomas in comparison with colorectal normal mucosa.
A gene expression and pre-mRNA splicing signature that marks the adenoma-adenocarcinoma progression in colorectal cancer.
Specimen part
View SamplesFasting is the process of metabolic adaption to food deprivation that is taking place in most organisms, e.g. during the daily resting phase in mammals. Furthermore, in biomedical research fasting is used in most metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular players in fasting. In this study we investigated the transcriptome signature of white adipose tissue, liver, and skeletal muscle in 24 hours fasted mice (and chow fat controls) using Affymetrix whole-genome microarrays.
Metabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues.
Sex, Specimen part
View SamplesHere we investigated the effect of stable knock-down of the NAA-catabolizing enzyme, Aspartoacylase (Aspa), on global gene expression in a brown adipocyte cell line.
N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes.
No sample metadata fields
View SamplesAbhd15 is mainly expressed in white adipose tissues and highly upregulated upon adipogenesis. Abhd15 expression is correlated with insulin resistance in obese humans, however its physiological function remains unknown. We used the microarray technology to gain insight into ABHD15s physiological function by identifying dysregulated genes in eWAT from Abhd15-ko mice in comparison to WT mice.
Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.
Sex, Specimen part
View SamplesIn addition to lipid second messengers derived from the plasma membrane, increasing evidence supports the existence of nuclear lipid-dependent signaling networks. Diacylglycerol is a key second messenger, generated at the nuclear level, which is metabolized by diacylglycerol kinases (DGKs). It has been demonstrated that nuclear DGK- negatively regulates cell cycle progression. The aim of this study was to identify key determinants of nuclear DGK--dependent cell cycle arrest in C2C12 mouse myoblasts. Using DNA microarrays, Real-Time RT-PCR and western blot, we demonstrated that nuclear DGK- downregulated the expression of cyclin D1 and increased the expression of TIS21/BTG2/PC3, a transcriptional regulator of cyclin D1 with a strong anti-proliferative function. Overexpression of TIS21/BTG2/PC3 blocked the cells in G1 phase of the cell cycle and decreased the levels of Ser807/811 phosphorylated retinoblastoma protein, similarly to overexpression of DGK-. Moreover, during myogenic differentiation of C2C12 cells, we showed an increase of TIS21/BTG2/PC3 expression and a decrease in cyclin D1 levels. siRNA downregulation of TIS21/BTG2/PC3 impaired myogenic differentiation by opposing cell cycle arrest. In summary, these data identify TIS21/BTG2/PC3 and cyclin D1 as downstream effectors of the nuclear DGK- and highlight the importance of this DGK isoform in the regulation of myoblast proliferation and differentiation.
TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest.
No sample metadata fields
View SamplesWe perfomed single-cell RNA-sequnecing of around 10,000 cells from normal human liver tissue to construct a human liver cell atlas. We reveal previously unknown subtypes in different cell type compartments. We also use our normal liver cell atlas to infer perturbed phenoytpes of cells from HCC samples, human cells engrafted into a mouse liver and liver organoids. Overall design: Single cells were isolated from human liver resection specimens and then sorted by FACS into 384 well plates in a unbiased way and on the basis of cell surface markers for distinct cell types. ScRNA-seq was done using the mCelSeq2 protocol cellbarcodes_cellid.csv Supplemetary file contains cellds and one of the 192 unique cellbarcode associated with the cellid.
A human liver cell atlas reveals heterogeneity and epithelial progenitors.
Specimen part, Subject
View SamplesGene expression in blood of children with autism spectrum disorder (ASD) was studied. Transcriptional profiles were compared with age and gender matched, typically developing children from the general population (GP) or IQ matched children with mental retardation or developmental delay (MR/DD).
Gene expression changes in children with autism.
No sample metadata fields
View SamplesPediatric Acute Myeloid Leukemia (AML) is an aggressive and poor prognosis malignancy for which there are few effective targeted approaches, despite the numerous genetic alterations, including MLL gene rearrangements (MLL-r). The histone methyltransferase DOT1L is involved in supporting proliferation of MLL-r cells, for which a target inhibitor, Pinometostat, has been evaluated in a clinical trial recruiting pediatric MLL-r leukemic patients. However, modest clinical effects have been reported. Recent studies reported that additional leukemia subtypes lacking MLL-r are sensitive to DOT1L inhibition. Here we report that targeting DOT1L with Pinometostat sensitizes pediatric AML cells to further treatment with the multi-kinase inhibitor Sorafenib, irrespectively of MLL-r. DOT1L pharmacologic inhibition induces AML cell differentiation and modulated expression of genes with relevant roles in cancer development. Such modifications in transcriptional program impact on further treatments, inducing a strong sensitization to Sorafenib, with increased apoptosis and growth suppression of both AML cell lines and primary pediatric AML cells with diverse genotypes. We used microarrays to define differential regulation of gene expression in AML cell lines with or without MLL gene rearrangements following pharmacologic inhibition of DOT1L.
Inhibition of Methyltransferase DOT1L Sensitizes to Sorafenib Treatment AML Cells Irrespective of <i>MLL</i>-Rearrangements: A Novel Therapeutic Strategy for Pediatric AML.
Treatment
View SamplesAt present, medical treatments of synchronous and metachronous liver metastases from colorectal cancer are not differentiated. The aim of the study was to analyze the gene expression profiling of synchronous and metachronous lesions in order to identify molecular signatures as possible basis for choice of systemic therapies. Fresh tissues specimens from metastases of 18 patients undergone liver surgery were collected (10 synchronous and 8 metachronous lesions). Gene expression profiling was studied using Affymetrix platform. Two different profiles were identified. Pathway related to the Epidermal Growth Factor receptor (EGFr) was upregulated in metachronous lesions whereas pathways mainly related to inflammation in synchronous lesions. Real Time-PCR, Western Blotting and ELISA confirmed that the metachronous lesions had the overexpression of EGFr, but the synchronous ones had the overexpression of Cyclo-oxygenase 2 (COX-2). These results suggest that synchronous or metachronous liver metastases from colorectal cancer could be differently treated on the basis of different molecular pathways.
Gene expression profiling of liver metastases from colorectal cancer as potential basis for treatment choice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line, Treatment
View Samples