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accession-icon GSE73331
Analysis of initial step of multiciliogenesis during the differentiation of adult airway progenitors
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Multiciliated cells are crucial for fluid and ion transport in epithelia of a variety of organs and their impaired development and function are seen in human diseases affecting the brain, respiratory, and reproductive tracts. Multiciliogenesis requires activation of a specialized transcription program coupled to complex cytoplasmic events that lead to large-scale centriole amplification to generate multicilia. Yet, it remains unclear how these events are coordinated to initiate multiciliogenesis in epithelial progenitors. Here we identify an unsuspected mechanism orchestrated by the transcription factor E2f4 essential to integrate these processes. We show that after inducing a transcriptional program of centriole biogenesis, E2f4 translocates to the cytoplasm to become a core component of structures classically identified as fibrous granules (FG), acting as organizing centers for deuterosome assembly and centriole amplification. Remarkably, loss of cytoplasmic E2f4 prevents FG aggregation, deuterosome assembly and multicilia formation even when E2f4s transcriptional function is preserved. Moreover, in E2f4-deficient cells multiciliogenesis is rescued only if both nuclear and cytoplasmic E2f4 activities are restored. Thus, E2f4 integrates previously unrelated nuclear and cytoplasmic events of the multiciliated cell program.

Publication Title

Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis.

Sample Metadata Fields

Specimen part

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accession-icon SRP090454
LBO D170
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

No description.

Publication Title

No associated publication

Sample Metadata Fields

Sex, Specimen part, Cell line

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accession-icon SRP073749
LBO D25
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

RNAseq data from EPCAM+ and EPCAM- population in D25 LBOs.

Publication Title

No associated publication

Sample Metadata Fields

Sex, Specimen part, Cell line

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accession-icon GSE22647
Adenosine 5 monophosphate-activated protein kinase regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 mitogen-activated protein kinase.
  • organism-icon Rattus norvegicus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, while AMPK is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive GILZ, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Since increased action of glucocorticoids is associated with development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacologic interventions to these pathologies.

Publication Title

AMPK regulates metabolic actions of glucocorticoids by phosphorylating the glucocorticoid receptor through p38 MAPK.

Sample Metadata Fields

Sex

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accession-icon GSE29912
The effect of GW3965 and dexamethasone on gene expression of rat livers
  • organism-icon Rattus norvegicus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

GLUCOCORTICOIDS are steroid hormones that strongly influence intermediary carbohydrate metabolism by increasing the transcription rate of glucose-6-phosphatase (G6Pase) a key enzyme of gluconeogenesis, and suppress the immune system which makes them one of the most important therapeutic agents in the treatment of allergic, autoimmune and inflammatory diseases. The biologic actions of circulating glucocorticoids are transmitted to the cells nucleus by the glucocorticoid receptor (GR). The nuclear liver X receptors (LXRs) bind to cholesterol metabolites, heterodimerize with the retinoid X receptor (RXR), and regulate the cholesterol turnover, the hepatic glucose metabolism by decreasing the expression of G6Pase, and repress a set of inflammatory genes in immune cells. The aim of this study is to evaluate the crosstalk between the GR- and LXR-mediated signaling systems. Transient transfection-based reporter assays and gene silencing methods using siRNAs for LXRs showed that overexpression/ligand (GW3965) activation of LXRs/RXRs repressed GR-stimulated transactivation of certain glucocorticoid response element (GRE)-driven promoters in a gene-specific fashion. Activation of LXRs by GW3965 attenuated dexamethasone-stimulated elevation of circulating glucose in rats and suppressed dexamethasone-induced mRNA expression of hepatic glucose-6-phosphatase (G6Pase) in rats, mice and human hepatoma HepG2 cells. In microarray transcriptomic analysis of rat liver, GW3965 differentially regulated glucocorticoid-induced transcriptional activity of about 15% of endogenous glucocorticoid-responsive genes. Mechanistically, and in vitro chromatin immunoprecipitation assay, we found that LXR/RXR bound GREs and inhibited GR binding to these DNA sequences in a gene-specific fashion. These novel results were further confirmed in in vivo binding assays, and in gel mobility shift assays, where recombinant LXR/RXR proteins were used to examine their interaction with classic or G6Pase GREs. We propose that administration of LXR agonists may be beneficial in glucocorticoid treatment- or stress-associated dysmetabolic states by directly attenuating the transcriptional activity of the GR on glucose and/or lipid metabolism.

Publication Title

Liver x receptors regulate the transcriptional activity of the glucocorticoid receptor: implications for the carbohydrate metabolism.

Sample Metadata Fields

Specimen part

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accession-icon GSE8481
Various human cell types
  • organism-icon Homo sapiens
  • sample-icon 63 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

We performed the GeneChip analysis to identify multiple extracellular determinants such as cytokines, cell membrane-bound molecules, and matrix responsible for cardiomyogenic differentiation, and evaluated the statistical significance of differential gene expression by the NIA array analysis (http://lgsun.grc.nia.nih.gov/ANOVA/) (Bioinformatics 21: 2548), a web-based tool for microarrays data analysis.

Publication Title

Gremlin enhances the determined path to cardiomyogenesis.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE11510
Taxonomy of placenta cells
  • organism-icon Homo sapiens
  • sample-icon 17 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The placenta is considered one of the candidate cell sources in cellular therapeutics because of a large number of cells and heterogenous cell population with myogenic potentials. We first analyzed myogenic potential of cells obtained from six parts of the placenta, i.e., umbilical cord, amniotic epithelium, amniotic mesoderm, chorionic plate, villous chorion (chorion frondosum), , and decidua basalis. Implantation of placenta-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of human dystrophin. Co-existence of human and murine nuclei in one myotube and presence of human dystrophin in murine myotube suggests that human dystrophin expression is due to cell fusion between host murine myocytes and implanted human cells. In vitro analysis revealed that cells derived from amniotic mesoderm, chorionic plate, ,and villous chorion efficiently transdifferentiate into myotubes. These cells fused to C2C12 murine myoblasts by in vitro co-culturing, and murine myoblasts start to express human dystrophin after fusion. These results demonstrate that placenta-derived cells, especially extraembryonic mesodermal cells, have a myogenic potential and regenerative capacity of skeletal muscle. Determination of cell specification with the gene chip analysis revealed that each placental cell has a distinct expression pattern.

Publication Title

No associated publication

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE10934
Human sclera
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The sclera maintains and protects the eye ball, which receives visual inputs. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. We have here demonstrated microarray data of cultured human scleral cells.

Publication Title

Human sclera maintains common characteristics with cartilage throughout evolution.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE17368
Epiphyseal cartilage
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Chondrocytes from extra fingers exhibited a high proliferative capacity: the cells reached to population doublings (PD) 30-35 within 4 weeks before replicative senescence. The propagated cells formed hyaline cartilage at 2 weeks after subcutaneous implantation of NOD/Scid/IL-2 receptor gamma knock out (NOG) mice, and the generated cartilage showed enchondral ossification at 8 to 12 weeks. The cartilage formation with osteogenesis depends on the number of cell division in vitro.

Publication Title

No associated publication

Sample Metadata Fields

Specimen part

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accession-icon GSE8113
Pooh cells
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

POU5F1 (more commonly known as Oct-4/3) is one of the stem cell markers and affects direction of differentiation in embryonic stem cells. To investigate whether cells of mesenchymal origin acquire embryonic phenotype, we generated a human cell line of mesodermal origin with overexpression of the chimeric POU5F1 gene with physiological co-activator EWS, which is driven by the potent EWS promoter by translocation. The cell line termed Pooh (POU5F1/Oct-4/3 overexpressing human) cells expressed embryonic stem cell genes such as Nanog and also non-translocated POU5F1, lost mesenchymal phenotypes, and exhibited embryonal stem cell-like alveolar structure when implanted into the subcutaneous tissue of immunodeficient mice. Hierarchical analysis by microchip analysis and cell surface analysis revealed that Pooh cells are subcategorized into the group of human embryonic stem cells and embryonal carcinoma cells. These results imply that cells of mesenchymal origin can partially be traced back to cells to embryonic phenotype by the POU5F1 gene in collaboration with the potent cis-regulatory element and the fused co-activator.

Publication Title

Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS.

Sample Metadata Fields

No sample metadata fields

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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