Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Sex, Age
View SamplesThe wheat gene Lr34 (Yr18/Pm38/Sr57/Ltn1) encodes a putative ABCG-type of transporter and is a unique source of disease resistance providing durable and partial resistance against multiple fungal pathogens. Lr34 has been found to be functional as a transgene in barley.
The wheat resistance gene Lr34 results in the constitutive induction of multiple defense pathways in transgenic barley.
Specimen part
View SamplesThe mycotoxin deoxynivalenol (DON) is a secondary metabolite from Fusarium species and is frequently present on wheat and other cereals. The main effects of DON are a reduction of the feed intake and reduced weight gain of broilers. At the molecular level DON binds to the 60S ribosomal subunit and inhibits subsequently protein synthesis at the translational level. It has been suggested that cells and tissues with high protein turnover rate, like the liver and small intestine, are most affected by DON. However, little is known about other effects of DON e.g. at the transcriptional level. Therefore we decided to perform a microarray analysis, which allows us the investigation of thousands of transcripts in one experiment.
Fusarium mycotoxin-contaminated wheat containing deoxynivalenol alters the gene expression in the liver and the jejunum of broilers.
Age, Specimen part, Treatment
View SamplesPtf1a was identified as the essential transcription factor which controls pancreatic exocrine enzyme expression. With lineage tracing eperiments Ptf1a was recognized as an important pancreatic progenitor transcription factor and Ptf1a null mice do not develop a pancreas.
RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors.
Specimen part
View SamplesTime course of early development of peripheral nerve, from embryonic day 9.5 to postnatal day 0.
Efficient isolation and gene expression profiling of small numbers of neural crest stem cells and developing Schwann cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
No sample metadata fields
View SamplesTo model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
No sample metadata fields
View SamplesTo model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
No sample metadata fields
View SamplesGraft-versus-host disease (GvHD) is still one of the major complications following allogeneic stem cell transplantation (SCT) triggered by alloreactive donor T cells. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the development of GvHD, data from the human system are rare mainly due to low cell numbers of circulating or organ-infiltrating Tregs in lymphopenic patients. Here, we present a comparative analysis of Tregs from patients with and without acute/ chronic GvHD designed as a dynamical approach studying the whole genome profile over the first 6 months after SCT. For this purpose, blood samples were collected monthly for FACS-based isolation of CD4+CD25highCD127low/- Tregs. The Treg transcriptome showed a high stability in the first half year representing the most sensitive time window for tolerance induction. However, the comparison of the Treg transcriptome from patients with and without GvHD uncovered regulated gene transcripts that point to a reduced suppressive function of Tregs with diminished migration capacity to the target organs likely contributing to the development of GvHD. These findings highlight the critical role of human Tregs in the pathophysiology of GvHD and identify novel targets for the manipulation of Tregs to optimize cellular immune intervention strategies.
Human regulatory T cells in allogeneic stem cell transplantation.
Specimen part, Disease, Disease stage, Time
View SamplesCoilin iCLIP data revealed 42 novel human snoRNAs of intronic origin. To validate their expression and estimate abundance of novel and annotated snoRNAs, we performed RNA-seq on polyA- and rRNA-depleted RNA isolated from HeLa cells. Results show that expression of novel snoRNAs is comparable to the previously annotated snoRNAs. Overall design: 1 replicate of RNA depleted of polyA and ribosomal RNA.
The coilin interactome identifies hundreds of small noncoding RNAs that traffic through Cajal bodies.
No sample metadata fields
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