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SRP124611
Mus musculus
19 Downloadable Samples
NextSeq 500
Description
Massively parallel single-cell RNA sequencing can precisely resolve cellular diversity in a high-throughput manner at low cost, but unbiased isolation of intact single cells from complex tissues, such as adult mammalian brains, is challenging. Here, we integrate sucrose-gradient assisted nuclei purification with droplet microfluidics to develop a highly scalable single-nucleus RNA-Seq approach (sNucDrop-Seq), which is free of enzymatic dissociation and nuclei sorting. By profiling ~18,000 nuclei isolated from cortical tissues of adult mice, we demonstrate that sNucDrop-Seq not only accurately reveals neuronal and non-neuronal subtype composition with high sensitivity, but also enables in-depth analysis of transient transcriptional states driven by neuronal activity, at single-cell resolution, in vivo. Overall design: Single-nucleus RNA sequencing analysis of adult mouse cerebral cortex
Publication Title
Dissecting Cell-Type Composition and Activity-Dependent Transcriptional State in Mammalian Brains by Massively Parallel Single-Nucleus RNA-Seq.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global analysis of the relationship between JIL-1 kinase and transcription.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Profiling of changes in steady state RNA levels upon RNAi-mediated knockdown of the chromosomal kinase JIL-1 in Drosophila S2 cells.
Publication Title
Global analysis of the relationship between JIL-1 kinase and transcription.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Epigenetic mechanisms contribute to deregulated gene expression of hematopoietic progenitors in Myelodysplastic Syndromes (MDS). Hypomethylating agents are able to improve peripheral cytopenias in MDS patients. To identify critical gene expression changes induced by hypomethylating agents, we analyzed gene expression profiling (GEP) of myelodysplastic and normal CD34+ hematopoietic stem cells treated in vitro with or without decitabine. Four MDS and two untreated early stage Hodgkins lymphomas were analyzed for GEP. Mock treated CD34+ stem cells segregate according to diagnosis and karyotype. After decitabine treatment, gene expression changes were more consistent on MDS CD34+ cells with abnormal kayotype. Comparing decitabine-induced genes with those found down-regulated in mock-treated MDS cells, we identified a list of candidate tumor suppressor genes in MDS. By real-time RT-PCR we confirmed expression changes for three selected genes CD9, CXCR4 and GATA2 in 12 MDS patients and 4 controls. CD9 was widely repressed in most MDS CD34+ cell samples, although similar levels of methylation were found in both normal and MDS total bone marrows. CXCR4 promoter methylation was absent in total bone marrows from 36 MDS patients. In conclusion, changes in gene expression changes induced by hypomethylating treatment are more pronounced in CD34+ cells from abnormal karyotype.
Publication Title
Gene expression profiling of myelodysplastic CD34+ hematopoietic stem cells treated in vitro with decitabine.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epigenetic changes play a role in the pathogenesis of myeloid malignancies and hypomethylating agents have shown efficacy in these diseases. We studied the apoptotic effect, the genome-wide methylation and gene expression profiles in HL60 cells following decitabine treatment, using micro-array technologies. Decitabine treatment resulted in a decrease in global DNA methylation, corresponding to 4876 probeset IDs with significantly reduced methylation levels, while expression of 2583 IDs was induced. The integrated analysis identified 160 genes demethylated and upregulated by decitabine, mainly including development and differentiation pathways genes. Genes target of polycomb group protein regulation were overrepresented in this group. Apoptosis was induced by decitabine and apoptosis-specific PCR arrays more precisely indicated decitabine-induced upregulation of 13 apoptosis-related genes, in particular Dap-kinase 1 and Bcl2L10. Correspondingly, in primary patient samples, BCL2L10 was hypermethylated in 45% of AML, 43% of therapy-related myeloid neoplasms, 12% of MDS and in none of the controls.
Publication Title
Analysis of genome-wide methylation and gene expression induced by 5-aza-2'-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
PTPRD is a tumor suppressor of glioma that is frequently co-deleted with CDKN2A/p16. We show that Ptprd and p16 cooperate to promote gliomagenesis in the RCAS PDGFB / Nestin tv-A glioma mouse model.
Publication Title
Loss of the tyrosine phosphatase PTPRD leads to aberrant STAT3 activation and promotes gliomagenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small non-coding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has been so far elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A>G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA (BCYRN1), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A-mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease. Overall design: Gene expression profiling of Pol III transcripts in control and POLR3A-mutated cell lines (HEK293 and MO3.13) using RNA-seq and small RNA-seq; ChIP-seq of FLAG-tagged POLR3A-WT and mutated POLR3A-M852V
Publication Title
Leukodystrophy-associated <i>POLR3A</i> mutations down-regulate the RNA polymerase III transcript and important regulatory RNA <i>BC200</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas signicantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identied a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicates a signicant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target.
Publication Title
Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
SREBF-1c is a transcription factor regulating fatty acid biosynthesis. We have charaterized the impact of the abcence of SREBF-1c on the development of peripheral neuropathy
Publication Title
Lack of sterol regulatory element binding factor-1c imposes glial Fatty Acid utilization leading to peripheral neuropathy.
Sample Metadata Fields
Age
View Samples