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GSE4711
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Gametes rely heavily on post-transcriptional control mechanisms to regulate their differentiation. In eggs, the storage and selective temporal activation of maternal mRNAs is essential for normal development. In the male, transcription ceases during spermiogenesis necessitating the post-transcriptional regulation of many paternal mRNAs required for spermatid differentiation and spermatozoan function. Messenger RNAs that are being actively translated form polysomes. whereas translationally inactive mRNAs are often sequestered in ribonucleoproteins (RNPs). Here we combine polysome display and microarray analyses of RNP and polysome fractions of testes from prepuberal and adult mice to characterize the translation state of individual mRNAs as spermatogenesis proceeds.. Consistent with published reports, many post-meiotic mRNAs known to be translationally delayed shift from the RNPs into the polysomes, confirming the validity of this approach. In addition, based upon the criterion of movement from RNPs to polysomes, we detect another 742 mouse testicular genes showing dramatic shifts between RNPs and polysomes. One sub-group of 35 genes including the known translationally delayed Pgk2, are initially transcribed and translationally repressed in meiotic spermatocytes, and translated post-meiotically. This high-through-put approach defines the changing translation patterns of a large number of genes as male germ cells differentiate and identifies a new group of post-transcriptionally regulated meiotic transcripts for future study.
Publication Title
Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Epithelial-mesenchymal transition (EMT) is a pivotal process in development and disease. In carcinogenesis, various signaling pathways are known to trigger EMT by inducing the expression of EMT transcription factors (EMT-TFs) like SNAIL1, ultimately promoting invasion, metastasis and chemoresistance. However, how EMT is executed downstream of EMT-TFs is incompletely understood. Here, using human colorectal cancer (CRC) and mammary cell line models of EMT, we demonstrate that SNAIL1 critically relies on bone morphogenetic protein (BMP) signaling for EMT execution. This activity requires the transcription factor SMAD4 common to BMP/TGFβ pathways, but is TGFβ signaling-independent. Further, we define a signature of BMP-dependent genes in the EMT-transcriptome which orchestrate EMT-induced invasiveness, and are found to be regulated in human CRC transcriptomes and during EMT in vivo. Collectively, our findings substantially augment the knowledge of mechanistic routes whereby EMT can be effectuated, which is relevant for the conceptual understanding and therapeutic targeting of EMT processes.
Publication Title
Canonical BMP Signaling Executes Epithelial-Mesenchymal Transition Downstream of SNAIL1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Converting epithelial into mesenchymal cells through epithelial-mesenchymal transition (EMT) requires massive changes in gene expression. How this is brought about is currently not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anti-correlated in transcriptomes of colorectal tumors and cell lines. In two cellular EMT models, ectopically expressed Snail1 downregulates FOXA factors and directly represses FOXA1. To elucidate how FOXA factors contribute to the control of epithelial gene expression, we determined by ChIP-seq data analysis FOXA chromosomal distribution in relation to chromatin structural features characterizing distinct states of transcriptional activity. This revealed a preferential localization of FOXA1 and FOXA2 to transcriptional enhancers at signature genes that distinguish epithelial from mesenchymal colon tumors. To validate the significance of this association, we investigated the impact of FOXA factors on structure and function of transcriptional enhancers at the epithelial genes CDH1, CDX2 and EPHB3. Expression of dominant negative FOXA2 led to chromatin condensation at these enhancer elements. Site- directed mutagenesis of FOXA binding sites in reporter gene constructs and by genome- editing in situ impaired enhancer activity and completely abolished the active chromatin state of the EPHB3 enhancer. Conversely, expression of FOXA factors in cells with inactive CDX2 and EPHB3 enhancers led to chromatin opening and de novo deposition of the H3K4me1 and H3K27ac marks. These findings establish the pioneer function of FOXA factors at enhancer regions of epithelial genes and demonstrate their essential role in maintaining enhancer structure and function. Thus, by repressing FOXA family members, Snail1 targets transcription factors at strategically important positions in gene-regulatory hierarchies which may facilitate transcriptional reprogramming during EMT.
Publication Title
SNAIL1-mediated downregulation of FOXA proteins facilitates the inactivation of transcriptional enhancer elements at key epithelial genes in colorectal cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
IlluminaHiSeq2000
Description
The human cerebral cortex depends for its normal development and size on a precisely controlled balance between self-renewal and differentiation of diverse neural progenitor cells. Specialized progenitors that are common in humans, but virtually absent in rodents, called ‘outer radial glia’ (ORG), have been suggested to be crucial to the evolutionary expansion of the human cortex. We combined cell type-specific sorting with transcriptome-wide RNA-sequencing to identify genes enriched in human ORG, including targets of the transcription factor Neurogenin, and previously uncharacterized, evolutionarily dynamic, long noncoding RNAs. Single-cell transcriptional profiling of human, ferret, and mouse progenitors showed that more human RGC co-express proneural Neurogenin targets than in ferret or mouse, suggesting greater self-renewal of neuronal lineage-committed progenitors in humans. Finally, we show that activating the Neurogenin pathway in ferret RGC promotes delamination and outward migration. Thus, we find that the abundance of human ORG is paralleled by increased transcriptional heterogeneity of cortical progenitors. Overall design: Three biological replicates of human late mid-fetal cortex (18 to 19 weeks of gestation) were dissociated and immunolabeled. Apical and outer radial glial cells were purified by FACS and compared to an immunonegative population, predominantly neurons.
Publication Title
Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Ovis aries
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
Fracture healing is a highly complex regenerative process. The sheep is an important large-animal model for studying delayed fracture healing. Here we used next-generation sequencing (Illimuna GA IIx) for gene expression analysis (RNAseq) in two conditional groups - standard and delayed healing. In both groups sequential biopsies 7, 11, 14 and 21 days after surgery were collected from callus tissue and annalized. For all timepoints and conditions the samples were pooled (n=6), except for day 21 standard (n=5).
Publication Title
Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms.
Publication Title
PAX5 overexpression is not enough to reestablish the mature B-cell phenotype in classical Hodgkin lymphoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We used microarrays to identify genes differentially expressed between mouse RUNX2 -/- and wt embryonic humeri at stage E14.5
Publication Title
Detection of novel skeletogenesis target genes by comprehensive analysis of a Runx2(-/-) mouse model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: MYC is a transcription factor encoded by the c-MYC gene (thereafter termed MYC). MYC is key transcription factor involved in many central cellular processes including ribosomal biogenesis. MYC is overexpressed in the majority of human tumours including aggressive B-cell lymphoma especially Burkitt's lymphoma. Although Burkitt's lymphoma is a highlight example for MYC overexpression due to a chromosomal translocation, no global analysis of MYC binding sites by chromatin immunoprecipitation (ChIP) followed by global next generation sequencing (ChIP-Seq) has been conducted so far in Burkitt's lymphoma.
Publication Title
Deep sequencing of MYC DNA-binding sites in Burkitt lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Goals and objectives of this study: to identify genes preferentially induced in human CD4+CD25hi Treg cells following T-cell activation with potential role for stabililization & maintenance of the regulatory program.
Publication Title
GARP: a key receptor controlling FOXP3 in human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goals and objectives of this study: to identify genes of the Treg signature induced by consitutive expression of GARP or FOXP3 in antigen-specific Th cells with potential role for stabililization & maintenance of the regulatory program.
Publication Title
GARP: a key receptor controlling FOXP3 in human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples