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SRP182694
Homo sapiens
56 Downloadable Samples
Illumina HiSeq 4000
Description
Missense mutations in coding region of PDX1 predispose to type-2 diabetes mellitus as well as cause MODY through largely unexplored mechanisms. Here, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying heterozygous missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1P33T/+, PDX1C18R/+ mutations and engineered isogenic cell lines carrying homozygous PDX1P33T/P33T, PDX1C18R/C18R mutations and a heterozygous PDX1 loss-of-function mutation (PDX1+/-). Using an in vitro ß-cell differentiation protocol, we demonstrated that both PDX1P33T/+, PDX1C18R/+ and PDX1P33T/P33T, PDX1C18R/C18R mutations impair ß-cell differentiation and function. Furthermore, PDX1+/- and PDX1P33T/P33T mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1P33T/+ and PDX1P33T/P33T mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NEURONATIN, both involved in insulin synthesis and secretion. Our results reveal mechanistic details of how diabetes-associated PDX1 point mutations impair human pancreatic endocrine lineage formation and ß-cell function and contribute to pre-disposition for diabetes. Overall design: We performed RNA-seq of control and isogenic PDX1 mutant cell lines at PP stage
Publication Title
Point mutations in the PDX1 transactivation domain impair human β-cell development and function.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The experiment aims to identify transcriptional effects differences between periimplantitis, Parodontitis and healthy gingival tissue
Publication Title
Peri-implantitis versus periodontitis: functional differences indicated by transcriptome profiling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Since the discovery of adult neural stem cells, their exact identity is still under discussion. Moreover, the lack of a reproducible procedure to purify neural stem cells prospectively rather than by growing them in vitro has so far precluded their study at the transcriptome level. Here we demonstrate a novel procedure to prospectively isolate neural stem cells from the adult mouse subependymal zone on the basis of their GFAP- and prominin1-expression by fluorescence-activated cell sorting. All self-renewing, multipotent stem cells are contained in this fraction at 70% purity. The stem cell identity of these double-positive cells is further demonstrated in vivo, by using a novel split-Cre-technology for fate mapping.
Publication Title
In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 60 Downloadable Samples
Description
We investigated the occupancy of RNA PolII and INTS11 during the stimulation of EGF and compared with drug treated condition using inhibitors against MAPK pathway and Integrator. Additionally, we examined transcription by sequencing the chromatin-bound fraction of RNA. Overall design: We employed several cel lines in our experiment, including HELA, KRAS mutant lung cancer cell line A549 and BRAF mutatant melanoma cell line A375. The conditons we checked including EGF stimulation, MAPK pathway inhibition using BRAF, MEK or ERK inhibitiors, targeting INTS11 with RNAi or integrator inhibitor. We used RNA sequencing to measure the expression profile and CHIP sequencing to detect INTS11 and RNA PolII recruitment on chromatin.
Publication Title
Integrator orchestrates RAS/ERK1/2 signaling transcriptional programs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
WNT1/beta-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons including the Substantia nigra pars compacta (SNc) subpopulation, whose degeneration is a hallmark of Parkinsons Disease (PD). However, the precise functions of WNT/beta-catenin signaling in this context remain unknown. Using mutant mice, primary ventral midbrain (VM) cells and pluripotent stem cells (mouse embryonic stem cells and induced pluripotent stem cells), we show that Dickkopf 3 (DKK3), a secreted glycoprotein that modulates WNT/beta-catenin signaling, is specifically required for the correct differentiation of a rostrolateral mdDA precursor subset into SNc DA neurons.
Publication Title
Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Illumina HiSeq 1500
Description
We report here mRNA-seq data of adult male Drosophila head tissues. We compare two different ages: young and midlife as well as chm/chameau (CG5229) heterozygous mutants. Overall design: Comparison of ageing effect (young vs. midlife) in wild-type and mutant.
Publication Title
Life span extension by targeting a link between metabolism and histone acetylation in Drosophila.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Here we show that oral creatine (Cr) supplementation leads to increased life span in mice. Treated mice showed improved neurobehavioral performance, decreased accumulation of the aging pigment lipofuscin and upregulation of anti-aging genes in brain. As Cr is virtually free of adverse effects, it may be a promising food supplement for healthy aging in man.
Publication Title
Creatine improves health and survival of mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 27 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This study identifies genes that alter their expression in synchrony with the late third instar and prepupal pulses of 20E.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This study identifies those genes that are dependent on EcR for their proper regulation at the onset of metamorphosis in Drosophila melanogaster.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
To identify 20E-regulated genes, wandering third instar larvae were dissected and their organs were cultured in the presence of either no hormone, 20E alone, cycloheximide alone, or 20E plus cycloheximide for six hours.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples