We generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma. Overall design: examination of genome-wide genome-wide gene expression levels and comparison to phenotypes
DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Specimen part, Disease, Subject
View SamplesIntegrity of the cornea, the most anterior part of the eye is indispensable for vision. 45 million individuals are bilaterally blind and another 135 millions have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing with a vertical turnover of seven to fourteen days in many mammals3. Identification of slow cycling cells (label-retaining cells or LRCs) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea4; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in striking opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here, we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. In addition, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells; hence, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia.
Oligopotent stem cells are distributed throughout the mammalian ocular surface.
No sample metadata fields
View SamplesRemoval of the transcription factor SAP1a member of the Ternary Complex Factor (TCF) group of transcription factors which in conjunction with Serum Response Factor (SRF) has been shown to have a profound effect on positive selection in the thymus. When another TCF Elk1 is knocked out in mice there is no effect on positive selection unless it is on a Sap1a KO background where the phenotype is very severe. We have stimulated isolated double positive T cells (DPs) with anti-CD3 to mimic positive selection and compared basal and stimulated transcription across the four genotypes to discover the downstream targets of Sap1a involved in positive selection.
Ternary complex factors SAP-1 and Elk-1, but not net, are functionally equivalent in thymocyte development.
Sex, Age, Specimen part, Treatment
View SamplesMicroRNAs (miRNAs) are short noncoding RNA molecules regulating the expression of mRNAs. Target identification of miRNAs is computationally difficult due to the relatively low homology between miRNAs and their targets. We present here an experimental approach to target identification where the cartilage-specific miR-140 was overexpressed and silenced in cells it is normally expressed in separate experiments. Expression of mRNAs was profiled in both experiments and the intersection of mRNAs repressed by miR-140 overexpression and derepressed by silencing of miR-140 was identified. The intersection contained only 49 genes, although both treatments affected the accumulation of hundreds of mRNAs. These 49 genes showed a very strong enrichment for the miR-140 seed sequence implying that the approach is efficient and specific. 21 of these 49 genes were predicted to be direct targets based on the presence of the seed sequence. Interestingly, none of these were predicted by the published target prediction methods we used. One of the potential target mRNAs, Cxcl12, was experimentally validated by Northern blot analysis and a luciferase reporter assay.
Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140.
No sample metadata fields
View SamplesThe TLX1 and TLX3 transcription factor oncogenes play an important role in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL)1,2. Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This Systems Biology analysis defined TLX1 and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, network structure analysis of this hierarchical network identified RUNX1 as an important mediator of TLX1 and TLX3 induced T-ALL, and predicted a tumor suppressor role for RUNX1 in T-cell transformation. Consistent with these results, we identified recurrent somatic loss of function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 atop of an oncogenic transcriptional network controlling leukemia development, demonstrate power of network analysis to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor suppressor gene in T-ALL.
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Specimen part, Cell line
View SamplesTransgenic expression of key transcritpion factors inducing T-cell leukemias in mice.
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Specimen part
View SamplesThe experiment was designed in order to knock down the expression of TLX3 gene in T-ALL cell line
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Cell line
View SamplesThe experiment was designed in order to knock down the expression of TLX1 gene in T-ALL cell line
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Cell line
View SamplesThird instar larval eye discs provide an in vivo model for cell cycle exit studies. Posterior to the Second Mitotic Wave proliferation is absent in a wild type eye disc. Inactivating mutations in tumor suppressor-like genes can lead to genome wide changes in gene expression that allow for inappropriate bypass of cell cycle exit signals posterior to the Second Mitotic Wave.
Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit.
Specimen part
View SamplesTranscriptome analysis of high-grade human ovarian adenocarcinomas. The hypothesis tested in the present study was that two reciprocal pathways, namely oxidative stress response and fibrosis, enable to build a hierarchical cluster of ovarian patients.
miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response.
Specimen part, Disease stage
View Samples