This SuperSeries is composed of the SubSeries listed below.
Transcriptome analysis of human diabetic kidney disease.
Specimen part, Disease, Disease stage, Subject
View SamplesWe identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples.
Transcriptome analysis of human diabetic kidney disease.
Specimen part, Disease, Disease stage, Subject
View SamplesWe identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples.
Transcriptome analysis of human diabetic kidney disease.
Specimen part, Disease, Disease stage, Subject
View SamplesWe identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples.
Transcriptome analysis of human diabetic kidney disease.
Specimen part, Disease, Disease stage
View SamplesThe human EphA3 gene was discovered in a pre-B acute lymphoblastic leukemia (pre-B-ALL) using the EphA3-specific monoclonal antibody (mAb), IIIA4, which binds and activates both human and mouse EphA3. We use two models of human pre-B-ALL to examine EphA3 function, demonstrating effects on pre-B-cell receptor signaling. In therapeutic targeting studies, we demonstrated antitumor effects of the IIIA4 mAb in EphA3-expressing leukemic xenografts and no antitumor effect in the xenografts with no EphA3 expression providing evidence that EphA3 is a functional therapeutic target in pre-B-ALL. Here we show that the therapeutic effect of the anti-EphA3 antibody was greatly enhanced by adding an -particle-emitting 213Bismuth payload.
EphA3 as a target for antibody immunotherapy in acute lymphoblastic leukemia.
Cell line
View SamplesFlowering plants have immotile sperm that develop within pollen and must be carried to female gametes by a pollen tube. The pollen tube engages in molecular interactions with several cell types within the pistil and these interactions are essential for successful fertilization. We identified a group of three closely related pollen tube-expressed MYB transcription factors (MYB97, MYB101, MYB120), which are required for proper interaction of the pollen tube with the female gametophyte. These transcription factors are transcriptionally induced during growth in the pistil. They regulate a transcriptional network leading to proper differentiation and maturation of the pollen tube, promoting proper pollen tube-ovule interactions resulting in sperm release and double fertilization.
Three MYB transcription factors control pollen tube differentiation required for sperm release.
Specimen part
View SamplesWe investigated the specificity profiles of a variety of RNA guided adenosine deaminases while exploring roles of NLS/NES and hyperactive mutants via analysis of the transcriptome-wide off-target A->G editing effected by these tools. To this end, HEK 293T cells were transfected with each construct and analyzed by RNA-seq. Untransfected cells were included as controls. From each sample, we collected ~40 million uniquely aligned sequencing reads. We then used Fisher's exact test to quantify significant changes in A->G editing yields, relative to untransfected cells, at each reference adenosine site having sufficient read coverage. The number of sites with at least one A->G editing event detected in any of the samples was computed. Overall design: Study of transcriptome wide A->G off-targets arising due to the overexpression of a variety of RNA guided adenosine deaminases.
In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.
No sample metadata fields
View SamplesTo identify transcripts altered upon LIN-41 knockdown, we transfected either a control siRNA or one of two different LIN-41 siRNAs into human embryonic stem cells and collected total RNA 72 hours after transfection. Overall design: We compared transcript levels between control siRNA or LIN-41 siRNA treated cells.
The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes.
No sample metadata fields
View SamplesInflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis.
MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.
Specimen part, Disease, Disease stage
View SamplesCells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENCODE project for factors that correlated with changes in transcription and identified binding of several components of the Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes repressed by hypoxia. SIN3A interference revealed that it participates in the downregulation of 75% of the hypoxia-repressed genes in endothelial cells. Unexpectedly, it also blunted the induction of 47% of the upregulated genes, suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq experiments showed that SIN3A preferentially localizes to the promoter region of actively transcribed genes and that SIN3A signal was enriched in hypoxia-repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our results reveal a prominent role for SIN3A in the transcriptional response to hypoxia and suggest a model where modulation of the associated histone deacetylase activity, rather than its recruitment, determines the transcriptional output. Overall design: Exponentially growing non-synchronized HUVEC were exposed to normoxia or hypoxia (21% or 1% oxygen respectively) for 8 hours and pulse-labelled with 4-thiouridine during the last two hours of treatment. RNA was extracted from samples in each condition (total RNA) and an aliquot was subjected to affinity chromatography to purify the 4-thiouridine-labelled (newly transcribed RNA, Newly Tr) and non-labelled (Pre-existent) RNA fractions. All three RNA fractions (total, newly transcribed and pre-existent) from each sample were analyzed by high-throughput sequencing. Submission includes 12 samples corresponding to 3 independent biological replicates.
The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia.
Cell line, Treatment, Subject
View Samples