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SRP045664
Homo sapiens
3 Downloadable Samples
IonTorrentProton
Description
We describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. Overall design: mRNA sequencing on peripheral blood from a family trio (mother, father and proband) where parents were asymptomatic and proband had severe neonatal anemia.
Publication Title
KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
The nuclear exosome performs critical functions in non-coding RNA processing, and in diverse surveillance functions including the quality control of mRNP formation, and in the removal of pervasive transcripts. Most non-coding RNAs and pervasive nascent transcripts are targeted by the Nrd1p-Nab3p-Sen1p (NNS) complex to terminate Pol II transcription coupled to nuclear exosome degradation or 3´-end trimming. Prior to nuclear exosome activity, the Trf4p-Air2p-Mtr4p polyadenylation complex adds an oligo-A tail to exosome substrates. Inactivating exosome activity stabilizes and lengthens these A-tails. We utilized high-throughput 3´-end poly(A)+ sequencing to identify at nucleotide resolution the 3´ ends targeted by the nuclear exosome, and determine the sites of NNS-dependent termination genome-wide. Overall design: 3´-end mapping of wild-type and various nuclear exosome mutant strains, either using gene knockouts or the anchor away system to conditionally deplete FRB-tagged proteins from the nucleus
Publication Title
Common genomic elements promote transcriptional and DNA replication roadblocks.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The second heart field (SHF) comprises a population of mesodermal progenitor cells that are added to the nascent linear heart to give rise to the majority of the right ventricle, interventricular septum, and outflow tract of mammals and birds. The zinc finger transcription factor GATA4 functions as an integral member of the cardiac transcription factor network in the SHF and its derivatives. In addition to its role in cardiac differentiation, GATA4 is also required for cardiomyocyte replication, although the transcriptional targets of GATA4 required for proliferation have not been previously identified. In the present study, we disrupted Gata4 function exclusively in the SHF and its derivatives. Gata4 SHF knockout mice die by embryonic day 13.5 and exhibit hypoplasia of the right ventricular myocardium and interventricular septum and display profound ventricular septal defects. Loss of Gata4 function in the SHF results in decreased myocyte proliferation in the right ventricle, and we identify numerous cell cycle genes that are dependent on Gata4 by microarray analysis. We show that Gata4 is required for Cyclin D2 expression in the right ventricle and that the Cyclin D2 promoter is bound and activated by GATA4 via three consensus GATA binding sites. These findings establish Cyclin D2 as a direct transcriptional target of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes.
Publication Title
GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Changes in Treg function are difficult to quantify due to the lack of Treg-exclusive markers in humans and the complexity of functional experiments. We sorted naive and memory human Tregs and conventional T cells, and identified genes that identify human Tregs regardless of their state of activation. We developed this Treg signature using Affymetrix human genome U133A 2.0 microarrays.
Publication Title
A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
analyzed changes in cytokine/chemokine production and gene expression levels in, human peripheral blood mononuclear cells upon teratment with 15M,2,4-benzenetriol
Publication Title
Identification of human cell responses to benzene and benzene metabolites.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
We report the effects of Rapamycin treatment on the transcriptome of normal human dermal fibroblasts isolated from foreskin (designated 2DD). We sequenced mRNA from 2 replicates of proliferative (PRO) quiescent (QUI, serum starved) or treated with 500nM Rapamycin for 5 days (RAP). Comparative analyses with PRO transcripts a baseline indicate that genes that changed expression from Rapamycin treated fibroblasts are significantly different from those of quiescence cells. Rapamycin treated cells showed a significant enrichment for cytokines from the Il-6 cascade. Overall design: Examination of mRNAs from proliferative, quiescent (serum starvation) and Rapamycin (5oonM, 5days) treated 2DD normal human dermal/foreskin fibroblasts.
Publication Title
Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In this study we plan to compare the profiles of control sample (cultured podocytes) with the Exoc5 knock down in cutured podocytes to examine the differentially expressed genes. Overall design: We hope to identify the genes that are downregulated on knocking down Exoc5 in cultured human podocytes cells
Publication Title
Disruption of the exocyst induces podocyte loss and dysfunction.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We performed gene expression profile of different B cell populations found in old (18 months old) C57BL/6 female mouse (B1 cells were recovered from both young and old C57BL/6 mice). Mice were nave and healthy (no autoimmunity was detected at the time of the experiment).
Publication Title
Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c⁺ B-cell population is important for the development of autoimmunity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Gallus gallus
- 8 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Inner ear auditory and vestibular tissues differ in their responses to mechanical stimuli.
Publication Title
Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To evaluate gene expression profiles on different dendritic cell subsets isolated from spleens of mice
Publication Title
CD28 Deficiency Enhances Type I IFN Production by Murine Plasmacytoid Dendritic Cells.
Sample Metadata Fields
Sex
View Samples