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SRP076703
Mus musculus
12 Downloadable Samples
Illumina HiScanSQ
Description
Purpose: Citron kinase (CitK) knockout mice show a severe form of primary microcephaly, associated with ataxia and lethal epilepsy. This phenotype is caused by massive apoptosis occuring during embryonic and post-natal brain development, associated with cytokinesis failure. Cerebellum is the tissue showing highest sensitivity to CitK loss. The clinical phenotype of CitK knockout mice is significantly resued by P53 inactivation. In addition, CitK/P53 double knockout brains have almost normal levels of apoptosis, but display high percentage of binucleated and multinucleated cells. The aim of this study was to analyze the gene expression changes produced in developing neural tissue by CitK loss and to determine which alterations are P53-dependent. expression changes Methods: We analyzed by RNA sequencing total RNA extracted from P4 cerebellum of mice characterized by the following genotypes: 1. CitK +/-, P53 +/- (CTRL); 2. CitK -/-, P53 +/- (CitK-KO); 3. CitK +/-, P53 -/- (P53-KO); 4. CitK -/-, P53 -/- (D-KO). Biological triplicates were analyzed per every genotype. Conclusions: The loss of CitK leads to a strong reduction of the expression of pro-neural genes and induces a P53-related pro-apoptotic gene sets. The analysis of D-KO mice reveals that most of these changes are P53-dependent, but many genes implicated in growth arrest are induced through P53-independent mechanisms. Overall design: Cerebellar mRNA profiles of 4-day old mice of CTRL, CitK-KO, P53-KO and D-KO mice were generated by deep sequencing, in triplicate, using Illumina HiScan SQ
Publication Title
ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individuals health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T and B cell activation pathways were differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and FcRIIB signaling associated with decreased anti-DENV specific antibody concentrations. Taken together, our data illustrate that symptom-free DENV infection in children is associated with determined by increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies
Publication Title
Increased adaptive immune responses and proper feedback regulation protect against clinical dengue.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Proprioception relies on two main classes of proprioceptive sensory neurons (pSNs). These neurons innervate two distinct peripheral receptors in muscle, muscle spindles (MSs) or Golgi tendon organs (GTOs), and synapse onto different sets of spinal targets, but the molecular basis of their distinct pSN subtype identity remains unknown.
Publication Title
The PDZ-domain protein Whirlin facilitates mechanosensory signaling in mammalian proprioceptors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Gallus gallus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We employ RNA-seq of FACS sorted cell populations to identify genes that are enriched in cranial neural crest in relationship to the trunk. Overall design: Transcriptional profiling of delaminating cranial and trunk neural crest subpopulations.
Publication Title
Reprogramming of avian neural crest axial identity and cell fate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 33 Downloadable Samples
- Illumina HiSeq 2000
Description
During transcription initiation, the TFIIH-kinase Kin28/Cdk7 marks RNA polymerase II (Pol II) by phosphorylating the C-terminal domain (CTD) of its largest subunit. Here we describe a structure-guided chemical approach to covalently and specifically inactivate Kin28 kinase activity in vivo. This method of irreversible inactivation recapitulates both the lethal phenotype and the key molecular signatures that result from genetically disrupting Kin28 function in vivo. Inactivating Kin28 impacts promoter release to differing degrees and reveals a “checkpoint” during the transition to productive elongation. While promoter-proximal pausing is not observed in budding yeast, inhibition of Kin28 attenuates elongation-licensing signals, resulting in Pol II accumulation at the +2 nucleosome and reduced transition to productive elongation. Furthermore, upon inhibition, global stabilization of mRNA masks different degrees of reduction in nascent transcription. This study resolves long-standing controversies on the role of Kin28 in transcription and provides a rational approach to irreversibly inhibit other kinases in vivo. Overall design: Total RNA was collected from wild-type and analog-sensitive Kin28 strains treated with reversible inhibitor 1-NAPP-1, irreversible inhibitor CMK, and solvent control DMSO. Equivalent ratios of S. pombe : S. cerevisiae cells were added to each sample before RNA extraction for normalization of read counts after sequencing. Nascent RNA was purified from total RNA by 4-thiouracil labeling, biotinylation, and streptavidin-pulldown. As a negative control, nascent RNA was also extracted from total RNA from cells that had not been treated with 4-thiouracil.
Publication Title
Engineered Covalent Inactivation of TFIIH-Kinase Reveals an Elongation Checkpoint and Results in Widespread mRNA Stabilization.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens, Rattus norvegicus
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Objective: The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDHhigh) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDHhigh cells in ovarian cancer. Methods: We compared ALDHhigh to ALDHlow cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. Results: ALDHhigh cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDHhigh cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following drugable targets were consistently expressed in the ALDHhigh cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18 / FGFR3. Conclusions: Based on functional characterization, ALDHhigh ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified drugable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes.
Publication Title
Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Mouse ES cells were stably transduced with a lentivirus expressing either wild-type KBP or the stable mutant KBP(KK/RR) and maintained in self-renewing growth conditions. RNA-seq was performed to assess mRNA expression differences caused by the stabilization of KBP. Overall design: 6 samples [a triplicate set for ES cells expressing wild-type KBP and a triplicate set expressing KBP(KK/RR)] were analyzed.
Publication Title
The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We performed gene expression profiling of P1 and P5 back and tail dermis to uncover potential explanations for the differences in HF formation at different ages and in different body sites.
Publication Title
Inhibition of β-catenin signalling in dermal fibroblasts enhances hair follicle regeneration during wound healing.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of CD40 + IgM in vitro-stimulated (6 hours) murine relafl/flCD19-Cre (furtheron designated as RELA) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor RELA in activated B cells. Overall design: Splenic B cells from 12-week old relafl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Publication Title
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
Sample Metadata Fields
No sample metadata fields
View Samples