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GSE66193
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitors (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion. Gene array and reconstitution assays indicate that this effect can be attributed to the regulation of ECM components and ECM-modifying enzymes in aNPCs by PACAP. Our work suggests that PACAP regulates a bidirectional interaction between the aNPCs and their niche: PACAP modifies ECM production and remodeling, in turn the ECM regulates progenitor cell adherence. We speculate that PACAP may in this manner help restrict adult neural progenitors to the stem cell niche in vivo, with potential significance for aNPC function in physiological and pathological states.
Publication Title
PACAP Promotes Matrix-Driven Adhesion of Cultured Adult Murine Neural Progenitors.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 48 Downloadable Samples
NextSeq 500
Description
We report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait. Overall design: Examination of the expression profile of mice adipose tissues fed either standard (Std), High-fat/high-sucrose (HF/HS) or HF/HS + antioxidant formulation (AOF) for 180 days
Publication Title
Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Lineage specific transcription factors (TF) define and reinforce tissue specific cell types. For instance, stable endoderm progenitors were established from human ESC by constitutive expression of SOX7 or SOX17. We hypothesized that combinatorial expression of OCT4, SOX2 and KLF4together with the neural-lineage TF, Zic3, could directly convert fibroblasts into stable neuronal progenitor cells (NPC). Ensuing colonies predominantly expressed genes present in human NPC, as demonstrated by genome wide transcriptional analysis, and this phenotype could be maintained through many passages. When injected in immunodeficient mice, Zic3-induced (Zi)NPC form neuroendocrine tumors without evidence of mesoderm or endoderm. In vitro, ZiNPC spontaneously differentiated to neural cells only, and could be differentiated into astrocytes, oligodendrocytes and motor neuron lineages. In conclusion, addition of Zic3 during induced pluripotent stem cell (iPSC) generation, allows for the derivation of stable neural lineage progenitor cells.
Publication Title
Zic3 induces conversion of human fibroblasts to stable neural progenitor-like cells.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Treatment
View Samples- Homo sapiens
- 29 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
The histological grade of carcinomas describes the ability of tumor cells to organize differentiated epithelial structures and has prognostic impact. Molecular control of differentiation in normal and cancer cells relies on lineage-determining transcription factors (TFs) that activate the repertoire of cis-regulatory elements controlling cell type-specific transcriptional outputs. TF recruitment to cognate genomic DNA binding sites results in the deposition of histone marks characteristic of enhancers and other cis-regulatory elements. Here we integrated transcriptomics and genome-wide analysis of chromatin marks in human pancreatic ductal adenocarcinoma (PDAC) cells of different grade to identify first, and then experimentally validate the sequence-specific TFs controlling grade-specific gene expression. We identified a core set of TFs with a pervasive binding to the enhancer repertoire characteristic of differentiated PDACs and controlling different modules of the epithelial gene expression program. Defining the regulatory networks that control the maintenance of epithelial differentiation of PDAC cells will help determine the molecular basis of PDAC heterogeneity and progression. Overall design: Poly(A) fraction of the total RNA from human pancreatic ductal adenocarcinoma cell lines was extracted and subjected to by multiparallel sequencing. Experiments were carried out in unmodified cells in duplicate, genome edited clonal CFPAC1 cells (2 KLF5-deleted CRISPR-Cas9 clones, 3 ELF3-deleted CRISPR-Cas9 clones and 2 wt clones) and CFPAC1 cells ectopically expressing ZEB1 or empty vector control (in duplicate).
Publication Title
Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1MLL4) whose specific functions are largely unknown. By using a genomic approach, we found that in macrophages, MLL4 (also known as Wbp7) was required for the expression of Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired Pigp expression in Wbp7-/- macrophages abolished GPI anchor-dependent loading of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the coreceptor for lipopolysaccharide (LPS)
Publication Title
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The specific ablation of Rb1 gene in stratified epithelia (RbF/F;K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues, however RbF/F;K14cre;p107-/- mice die postnatally. Acute pRb loss in stratified epithelia, using an inducible mouse model (RbF/F;K14creERTM), shows that p107 exerts specific tumor suppressor functions in its absence. After simultaneous absence of pRb and p107, p53 transcriptional function is impaired and Pten expression is reduced. All mutant mice develop spontaneous squamous tumors carcinomas rapidly. Gene expression analysis of mouse tumors, besides supporting the impaired p53 function and the susceptibility to Akt/mTOR inhibitors, also revealed significant overlap with human squamous carcinomas. Thus, RbF/F;K14creERTM;p107-/- may constitute a new mouse model for these malignancies. Collectively, these data demonstrate the existence of a previously unreported functional connection between pRb, Pten and p53 tumor suppressors, through p107, of a particular relevance in squamous tumor development.
Publication Title
A novel tumor suppressor network in squamous malignancies.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The entorhinal cortex of the mouse seems to be sensitive to molecular mechanisms that have been linked to the pathology of Alzheimer's disease. In this microarray study we are interested in comparing the expression profile of the left versus the right EC of the mouse, in order to understand if there is a significant difference in gene expression that might reveal any insights into the differential activation of these areas.
Publication Title
Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 53 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Human type 1 diabetes (T1D) arises through autoimmunity towards the insulin-producing pancreatic cells and is modeled by the BioBreeding (BB) rat. Factors associated with islet autoimmunity are dilute and difficult to directly measure in the periphery. Therefore, we previously utilized microarray-based bioassay where human T1D sera were used to induce a disease-specific gene expression signature in unrelated, healthy peripheral blood mononuclear cells (PBMC).
Publication Title
Identification of a serum-induced transcriptional signature associated with type 1 diabetes in the BioBreeding rat.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: In this study, we identify global transcriptome alterations following removal of individual or multiple miR-196 family members in mouse. Next generation sequencing-derived transcriptome profiling (RNA-seq) was performed. Methods: A GFP reporter cassette was engineered to replace the mature miR-196a1 and miR-196a2 miRNA genomic loci in mouse (creating a knockout). GFP positive cells from an extensive knock-out allellic series of the three individual miR-196 genes, as detailed below, were isolated from E9.5 mouse embryos by FACS. miR-196b knockout cells were not marked with a fluorescent reporter and an assumption of co-expression with miR-196a2 was made. mRNA profiles were generated by deep sequencing in a minimum of four biological replicates per genotype, using an Illumina HiSeq 2000 instrument. Read information was mapped to the mouse genome and processed as described. Conclusions: Our study represents the first detailed analysis of embryonic transcriptomes following loss of single and multiple miR-196 family members. We identify complex dysregulation of many Hox genes, in addition to key developmental signalling pathways involved in somitogenesis. Overall design: mRNA profiles of E9.5 mouse embryos with miR-196 loss-of-function were generated by deep sequencing, in a minimum of four biological replicates, using Illumina HiSeq 2000.
Publication Title
Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs.
Sample Metadata Fields
No sample metadata fields
View Samples