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GSE48540
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
Publication Title
CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Human adipose-derived stem/stromal cells (hASCs) can differentiate into a large broad of specialized cell types to ensure homeostasis of tissues. Thus, they are drawing increasing attention in cell therapy and regenerative medicine. However, culture conditions are still critical to ensure their regenerative capabilities. Here we compared Standard conditions (αMEM containing 10% fetal bovine serum) and Endothelial cell Growth Medium 2 (EGM2) containing few serum (2% v/v) for expansion of hASCs. Both types of hASCs were exhaustively characterized by high throughput studies, Gene Set Enrichment Analyses (GSEA) and differentiation potentials experiments. EGM2-hASCs showed enhanced multipotency and their phenotype was more immature than Standard-hASCs. The adipogenic potential of EGM2-hASCs was clearly more extented, including toward the thermogenic beige adipocyte fate. Data from microarray and GSEA highlighted Transforming Growth Factor β1 (TGFβ1) as upstream factor influencing the becoming of Standard-hASCs which is consistent with higher TGFβ1 content in Standard medium. This was associated with nuclear SMAD3 localization and higher expression of its active form in Standard-hASCs. Moreover, these cells were primed into osteoblast, chondroblast and Vascular Smooth Muscle (VSM) lineages at the expense of their adipogenic potential. Their treatment with TGFβ1 receptor inhibitors resulted in a cytoplasmic re-localization of SMAD3 and a decrease of VSM and osteoblastic lineages markers, increasing in turn their beige adipogenic potential. Therefore, TGFβ1 is a key factor committing hASCs toward osteo-chondroblastic and VSM lineages at the expanse of their beige adipogenic potential. Thanks to low TGFβ1 content, EGM2 medium improves the maintenance of uncommitted hASCs with strong beige adipocyte potential.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling, but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs.
Publication Title
Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Guanabenz is an FDA approved drug for hypertension. It has been shown also to be an inhibitor of GADD34, the stress-inducible cofactor of PP1. GADD34 has been shown to play a key role in controlling cytokine production in MEFs and dendritic cells.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins involved in gene expression regulation, although their in vivo targets and activities in biological processes like cell differentiation, that requires reprogramming of gene expression programs at multiple levels, are not well characterized. In this report, we uncovered a new mechanism by which DDX5 and DDX17 cooperate with hnRNP H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms. We next observed that downregulation of DDX5 and DDX17 protein expression during epithelial to mesenchymal transdifferentiation and during myogenesis contributes to switching splicing programs during these processes. Remarkably, this downregulation is mediated by the production of microRNAs induced upon differentiation in a DDX5/DDX17-dependent manner. Since DDX5 and DDX17 also function as coregulators of master transcriptional regulators of differentiation, we propose to name these proteins master orchestrators of differentiation, that dynamically orchestrate several layers of gene expression.
Publication Title
RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (poly I:C), DCs mount a specific transcription program during which the growth arrest and DNA damage-inducible protein 34 (GADD34/MyD116), a phosphatase 1 (PP1) cofactor, is expressed. Together with its constitutively active counterpart CReP, GADD34 promotes an extensive dephosphorylation of the translation initiation factor eIF2-alfa in activated DCs. In turn, dephosphorylation of eIF2-alfa prevents the translation inhibition normally associated with cellular stress or detection of cytoplasmic double-stranded RNA. These observations have important implications in linking pathogen detection with the integrated stress responses molecular machinery. The importance of this regulation for DC function is exemplified by the alteration of IFN-beta production or the induction of caspase-3 cleavage upon inhibition of PP1 activity.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor / interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of important signal transduction molecules. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.
Publication Title
MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Paradoxical sleep function remains unknown although several studies indicate that it might play a role in learning and memory. To investigate what modifications paradoxical sleep may bring at the molecular level in neocortex and in hippocampal formation, we profiled gene expression in these structures in rats with different quantities of PS by cDNA microarrays approach.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 66 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular signatures of cardiac defects in Down syndrome lymphoblastoid cell lines suggest altered ciliome and Hedgehog pathways.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21.
Publication Title
Molecular signatures of cardiac defects in Down syndrome lymphoblastoid cell lines suggest altered ciliome and Hedgehog pathways.
Sample Metadata Fields
Sex, Specimen part
View Samples