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GSE81908
Mus musculus
10 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
In this study, we set out to identify those molecular features of the POU transcription factor Oct4 that are responsible for inducing pluripotency in somatic cells. Oct4 is known to have a strong preference to cooperate with Sox2 on heterodimeric SoxOct elements predominantly found in enhancers of genes expressed in embryonic stem cells (ESCs). To test whether this partnership is specific to Oct4, we compared its DNA recognition and reprogramming activities to the paralogous transcription factor Oct6, which cannot induce and maintain pluripotency in mouse cells. By analyzing ChIP-Seq data and performing quantitative dimerization assays, we found that in somatic cells, instead of heterodimerzing with Sox-factors, Oct6 more potently homodimerizes on OctOct elements. We identified that a single amino acid is crucial in directing binding to the respective composite DNA element. As a consequence, just changing this one amino acid hampers Oct4 in generating induced pluripotent stem cells (iPSCs). In contrast, the reverse mutation in Oct6 did not augment its reprogramming activity. This was achieved with at least two additional exchanges. In summary, we demonstrate that cell-type specific POU factor function is determined by a limited set of residues that affect DNA and partner factor interactions. Such relatively minor changes lead to a pronounced impact on regulatory function and reprogramming activity.
Publication Title
Changing POU dimerization preferences converts Oct6 into a pluripotency inducer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in hiPSC-derived neural progenitor cells (hiPSC-NPC) is sufficient to rapidly generate O4+ oligodendrocytes with an efficiency of 60 to 70% within 28 days.
Publication Title
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
Illumina Genome Analyzer IIx
Description
A total of 332 genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in ten human pterygium samples.
Publication Title
Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Genes were identified which modified their expression in a dose-dependent manner upon exposure to doxycycline. The more represented cellular pathways included all mitochondrial genes, the endoplasmic reticulum stress response, integrins and extracellular matrix components, and growth factors. Overall design: Examination of 4 different doses of doxycycline in three human pterygium samples.
Publication Title
Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 36 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused by Escherichia coli (E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure to E. coli lipopolysaccharide (LPS) treatment.
Publication Title
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) utilising subcutaneous adipose tissue-derived stromal vascular fraction (SAT-SVF) as a negative control population. Baseline gene expression in ECFC fully corresponds to their endothelial specification and may contribute to the basement membrane organisation, fulfilling the requirements for the suitable cell population for in vitro pre-endothelialisation of tubular scaffolds. Overall design: Comparison of gene expression in 4 cell types by Hiseq sequencing.
Publication Title
Human Peripheral Blood-Derived Endothelial Colony-Forming Cells Are Highly Similar to Mature Vascular Endothelial Cells yet Demonstrate a Transitional Transcriptomic Signature.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 321 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the hosts inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 95 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.82). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.94, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.
Publication Title
Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.
Sample Metadata Fields
Race
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Recent observations about how cells sense amino acids have argued for preeminent roles of mTOR and the stress kinase GCN2 in allowing cells to estimate their amino acid needs. Here we used models of programmed immune microenvironments where helper T cells have to sense how much amino acids are available to engage in antigen-fueled proliferation. Contrary to current models, T cells activate mTOR in the competency phase of the cell cycle regardless of amino acid amounts, GCN2 or surface TCR. Instead, we found T cells use an amino acid sensing system to target IL-2-induced STAT5 phosphorylation at the restriction point of cell cycle commitment. mTOR activity is subsequently reduced and specifically connected to SREBP activation. T cells can be pushed into cycle by increasing IL-2 even when no amino acids are available. Collectively, our studies reveal helper T cells use sequential and distinct pathways to measure local amino acid concentrations.
Publication Title
Proliferating Helper T Cells Require Rictor/mTORC2 Complex to Integrate Signals from Limiting Environmental Amino Acids.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Integrins facilitate intercellular movement and communication. Unlike the promiscuous activities of many integrins, 6 integrin is restricted to epithelia and partners exclusively with integrin V to modulate acute lung injury (ALI). Given that ALI is a complication of respiratory infection, we used mice lacking 6 integrin (6 KO) to probe the role of the epithelial layer in controlling the lung microenvironment during infection. We found 6 KO mice were protected from disease caused by influenza and Sendai virus infections. They were also protected from disease caused by Streptococcus pneumoniae infection alone and after prior influenza virus infection, the co-infection representing an often-lethal condition in humans. Resistance in the absence of epithelial 6 integrin was caused by intrinsic priming of the lung microenvironment by type I interferons through a mechanism involving transforming growth factor- regulation. Expression of 6 on epithelia suppresses the production of interferons, providing an advantage to the pathogen. Acute inhibition of 6 function may therefore provide a means to improve outcomes in lung microbial infections.
Publication Title
An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.
Sample Metadata Fields
Specimen part
View Samples