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GSE75444
Homo sapiens
2 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The epithelial-mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induced mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reversed these changes; as did silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibited similar metastases levels, but the cells with re-expressed H2A.X exhibited substantially elevated levels. We surmise that H2A.X re-expression led to partial EMT reversal and increased robustness in the HCT116 cells, permitting them to both form tumors and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlated inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a novel regulator of EMT.
Publication Title
The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of LDBM cells stimulated with IL-5
Publication Title
IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Lung alveolarization is a complex process that involves interactions between several cell types and leads to considerable increase in gas-exchange surface area. The step designated secondary septation includes elastogenesis from interstitial fibroblasts.
Publication Title
Gene expression profiling in lung fibroblasts reveals new players in alveolarization.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including eosinophil-lineage commitment (eosinophil progenitor [EoP] compared to granulocyte-monocyte progenitor [GMP]) and lineage maturation (eosinophil compared to EoP). Our analyses revealed markedly greater transcriptome alterations associated with eosinophil maturation (1199 genes) compared to eosinophil-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Our analyses also delineated a 976 gene eosinophil-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with eosinophils. Epigenomic studies revealed that genes that were specifically induced with eosinophil-lineage commitment in EoPs were “poised” with active chromatin marks in GMPs, despite not being expressed in GMPs. In contrast, a majority of the genes that were highly and specifically induced with maturation in eosinophils was not associated with poised chromatin, suggesting distinct epigenetic regulation between genes induced with lineage commitment compared to genes induced with cell maturation during eosinophil development. Overall design: RNA Seq and H3K4me3 distribution of GMPs, EoPs and eosinophils sorted from Balb/c bone marrow. RNA Seq libraries were prepared from 2 independent sorts of each cell type (GMP, EoPs, Eosinophils [Eos]). ChIP Seq was performed with chromatin from one sort of each cell type.
Publication Title
Transcription Factor Repertoire of Homeostatic Eosinophilopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer
Description
Eosinophils are major effector cells in type 2 inflammatory responses and become activated in response to IL-4 and IL-33, yet the molecular mechanism remains unclear. We examined the direct effect of these cytokines on eosinophils and demonstrated that murine eosinophils respond to IL-4 and IL-33 by phosphorylation of STAT-6 and NFkB, respectively. RNA sequencing analysis of murine eosinophils indicated that IL-33 regulates 519 genes, whereas IL-4 regulates only 28 genes, including 19 IL-33-regulated genes. Interestingly, IL-33 induced eosinophil activation via two distinct mechanisms, IL-4 independent and IL-4 secretion/auto-stimulation dependent. Anti-IL-4 or anti-IL-4Ra antibody-treated eosinophils, as well as Il4- or Stat6-deficient eosinophils, had attenuated protein secretion of a subset of IL-33-induced genes, including Retnla and Ccl17. However, the induction of most IL-33-regulated transcripts (e.g. Il6 and Il13) was IL-4 independent and blocked by NFkB inhibition. Indeed, IL-33 induced the rapid release of pre-formed IL-4 protein from eosinophils by an NFkB-dependent mechanism. Thus, we have identified a novel activation pathway in murine eosinophils that is induced by IL-33 and differentially dependent upon IL-4. These data suggest that IL-4 plays a critical role in auto-amplification of IL-33-induced eosinophil activation and could be a potential target for therapeutic approaches in IL-33-related eosinophil-associated diseases. Overall design: Low density bone marrow derived murine eosinophils were generated in culture over the period of 14 days. Eosinophils were activated by either IL-33 or IL-4 at 10 ng/ml for 1hr and 4hr. RNA was collected and subjected to next generation sequencing.
Publication Title
IL-33 markedly activates murine eosinophils by an NF-κB-dependent mechanism differentially dependent upon an IL-4-driven autoinflammatory loop.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Molecular mechanisms that are responsible for the development of human skin epithelial cells are not completely understood so far. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSC) remains poor. Using an approach including RNA interference and high-throughput imaging of early epithelial cells, we could identify candidate kinases which are involved in skin epithelial differentiation. Among them, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors, increased the amount of generated keratinocytes and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins. Our data bring substantial input in the regulation of human skin epithelial differentiation and for improving differentiation protocols from pluripotent stem cells.
Publication Title
An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Primitive neuro-ectodermal tumours (PNET) of the supratentorial region are rare, highly malignant embryonal brain tumours affecting young children. We recently highlighted the importance of a microRNA cluster housing miR-520g. We utilized the Illumina HumanWG-6 v3 R2 and HumanHT-12 v3 R2 Expression BeadChip platforms to profile the effects of miR-520g on gene expression.
Publication Title
Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 117 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Prostate organogenesis involves epithelial growth in response to inductive signalling from specialised subsets of mesenchyme. To identify regulators and morphogens active in mesenchyme, we performed transcriptomic analysis using Tag-seq, RNA-seq, and single cell RNA-seq and defined new mesenchymal subsets and markers. We documented transcript expression using Tag-seq and RNA-seq in female rat Ventral Mesenchymal Pad (VMP) as well as adjacent urethra comprised of smooth muscle and peri-urethral mesenchyme. Transcripts enriched in VMP were identified in Tag-seq data from microdissected tissue, and RNA-seq data derived from cell populations and single cells. We identified 400 transcripts as enriched or specific to the VMP using bio-informatic comparisons of Tag-seq and RNA-seq data. Comparison with single cell RNA-seq identified transcripts yielded 45 transcriptscommon to both approaches. Cell subset analysis showed that VMP and adjacent mesenchyme were composed of distinct cell types and that each tissue was comprised of two subgroups. Markers for these subgroups were highly subset specific. Thirteen transcripts were validated by qPCR to confirm cell specific expression in microdissected tissues, as well as expression in neonatal prostate. Immunohistochemical staining demonstrated that Ebf3 and Meis2 showed a restricted expression pattern in VMP condensed mesenchyme. Taken together, we demonstrate that the VMP shows limited cellular heterogeneity and that our high-resolution transcriptomic analysis identified new mesenchymal subset markers associated with prostate organogenesis. Overall design: Tag-sequencing, RNA-sequencing and single-cell RNA-sequencing on 2 female inductive mesenchymal tissues of the developing prostate/urogenital tract.
Publication Title
Identification of genes expressed in a mesenchymal subset regulating prostate organogenesis using tissue and single cell transcriptomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Recent genomic approaches have suggested the existence of multiple distinct subtypes of medulloblastoma. We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups. We determined gene expression profiles and DNA copy number aberrations for 103 primary medulloblastomas. Bioinformatic tools were used for class discovery of medulloblastoma subgroups based on the most informative genes in the dataset. Immunohistochemistry for subgroup-specific signature genes was used to determine subgroup affiliation for 294 non-overlapping medulloblastomas on two independent tissue microarrays (TMAs). Multiple unsupervised analyses of transcriptional profiles identified four distinct, non-overlapping molecular variants: WNT, SHH, Group C, and Group D. Supervised analysis of these four subgroups revealed significant subgroup-specific demographics, histology, metastatic status, and DNA copy number aberrations. Immunohistochemistry for DKK1 (WNT), SFRP1 (SHH), NPR3 (Group C), and KCNA1 (Group D) could reliably and uniquely classify formalin fixed medulloblastomas in ~98% of cases. Group C patients (NPR3 +ve tumors) exhibited a significantly diminished progression free and overall survival irrespective of their metastatic status. Our integrative genomics approach to a large cohort of medulloblastomas has identified four disparate subgroups with distinct demographics, clinical presentation, transcriptional profiles, genetic abnormalities, and clinical outcome. Medulloblastomas can be reliably assigned to subgroups through immunohistochemistry, thereby making medulloblastoma sub-classification widely available. Future research on medulloblastoma and the development of clinical trials should take into consideration these four distinct types of medulloblastoma.
Publication Title
Medulloblastoma comprises four distinct molecular variants.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- NextSeq 500
Description
Three different progenitor cell subsets in subcutaneous and visceral adipose tissues derived from 5 obese patients were subjected to AmpliSeq transcriptome profiling. Transcriptomic profiles were analyzed to compare progenitor cell subsets and the impact of subcutaneous and visceral adipose tissue location. Overall design: Transcriptomic profiling of 3 different progenitor cell types in subcutaneous and visceral adipose tissues derived from 5 obese patients (3X2X5=30 samples).
Publication Title
Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells.
Sample Metadata Fields
Subject
View Samples