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SRP078915
Mus musculus
6 Downloadable Samples
Illumina HiSeq 1500
Description
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Overall design: Transcriptome analysis in control vs. Uhrf1-deficient brain
Publication Title
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 1500
Description
In order to understand if early epigenetic mechanisms instruct the long-term behaviour of neural stem cells (NSCs) and their progeny, we examined the protein Uhrf1 as it is highly expressed in NSCs of the developing brain and rapidly downregulated upon differentiation. Conditional deletion of Uhrf1 in the developing cerebral cortex resulted in rather normal proliferation and neurogenesis but severe postnatal neurodegeneration. During development, deletion of Uhrf1 resulted in global DNA hypomethylation with a strong activation of the IAP family of endogenous retroviral elements, accompanied by an increase in hydroxy methyl cytosine. Downregulation of Tet enzymes rescued the IAP activation in Uhrf1 cKO cells, suggesting an antagonistic interplay between Uhrf1 and Tet on IAP regulation. As IAP upregulation persists into postnatal stages in the conditional Uhrf1 KO mice, our data show the lack of means to repress IAPs in differentiating neurons that normally never express Uhrf1. The high load of viral proteins and other transcriptional dysregulation ultimately lead to extensive postnatal neurodegeneration. Taken together, these data show that early developmental NSC factors can have long-term effects in neuronal differentiation and survival. Moreover, it highlights how specific the consequences of widespread changes in DNA methylation are for certain classes of retroviral elements. Overall design: Transcriptome analysis in control vs. Uhrf1-deficient brain
Publication Title
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- 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- Danio rerio
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
We compared transcriptomes of two ependymoglial populations isolated from adult zebrafish telencephalon. Overall design: Ependymoglial cells are acutely isolated from the adult zebrafish brains form 3 months old transgenic gfap:GFP animals. GFP is experssed in all ependymoglial cells and two populations are separated using GFP intensity in FACS.
Publication Title
The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing -cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far.
Publication Title
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Estrogen receptor- (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of this transcription factor using the Affymetrix Genechip Mouse Genome 430-2.0 arrays.
Publication Title
Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BMP3 stimulates mesenchymal stem cell proliferation, but the down-stream molecular targets of BMP3 are unknown
Publication Title
Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Bos taurus
- 12 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
Reproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early embryonic development. The ovarian-derived sex steroids estrogen and progesterone have been found to influence cell proliferation, differentiation and functionality of the oviduct. The objective of this study was to investigate steroidal regulation of oviductal epithelial cell function by using the Bovine Gene 1.0 ST array (Affymetrix Inc., CA) for transcriptional profiling. Our overall goals were to increase our understanding of known epithelial cell processes critical for fertility, and to identify novel genes and biochemical processes for future analysis. Transcripts were annotated using NetAffx annotation database for the Bovine gene 1.0 ST array and last updated in June 2014.
Publication Title
A transcriptomal analysis of bovine oviductal epithelial cells collected during the follicular phase versus the luteal phase of the estrous cycle.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 13 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
In many parts of the US, selenium (Se)-deficient soils dictate the necessity of supplementing this trace mineral directly to the diet of cattle, with the form of Se supplied known to affect tissue-level gene expression profiles and presumably function. Because a deficiency of Se will reduce fertility, including reduced biosynthesis of testosterone by the testis and an increased frequency of abnormalities in mature spermatozoa, we hypothesized that the form of Se supplemented to cows during gestation would affect the transcriptome of the neonatal bull calf testis. Microarray analysis using the Bovine gene 1.0 ST array (GeneChip; Affymetrix, Inc., Santa Clara, CA) was conducted to determine whether gestational form of supplemental Se affected gene expression profiles in the testis. GeneChip transcript annotations were last updated in January 2013 using the annotation update release 33 from the NetAffx annotation database.
Publication Title
Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways.
Sample Metadata Fields
Specimen part
View Samples