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GSE30028
Mus musculus
19 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs).
Publication Title
Pbx1 restrains myeloid maturation while preserving lymphoid potential in hematopoietic progenitors.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 88 Downloadable Samples
Illumina HiSeq 2500
Description
FSHD and control immortalised myoblasts show repression of Pax7 target genes Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.
Publication Title
PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Satellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved in acquisition of muscle stem cell characteristics.
Publication Title
Gene Expression Profiling of Muscle Stem Cells Identifies Novel Regulators of Postnatal Myogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 84 Downloadable Samples
- Illumina HiSeq 2500
Description
FSHD myoblasts show a suppression of ESRRA and PPARGC1A during myogenesis Overall design: FSHD Myoblasts 54-2, 54-12, 54-A5, 16A and 12A and matched controls 54-6, 54-A10, 16U and 12U were plated at 312,000 cells per 12 well plate in proliferation media and cultured for 48 hours or until 100% confluent, then induced to differentiate for 3.5 days, samples were taken at 8 time points during differentation for 54-6 and 54-12 and at confluency and terminal differentiation in the remaining lines. RNA-sequencing was performed on high quality (RIN > 8.0) DNA free RNA.
Publication Title
Dynamic transcriptomic analysis reveals suppression of PGC1α/ERRα drives perturbed myogenesis in facioscapulohumeral muscular dystrophy.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The NF-B pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic beta cell dysfunction in the metabolic syndrome. While canonical NF-B signaling is well studied, there is little information on the divergent non-canonical NF-B pathway in the context of pancreatic islet dysfunction in diabetes. Here, we demonstrate that pharmacological activation of the non-canonical NF-B inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. Further, we identify NIK as a critical negative regulator of beta cell function as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of non-canonical NF-B components p100 to p52, and accumulation of RelB. Tumor necrosis factor (TNF) and receptor activator of NF-B ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive beta cell intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the non-canonical NF-B transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to beta cell failure. These studies reveal that NIK contributes a central mechanism for beta cell failure in diet-induced obesity.
Publication Title
Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Doxycycline-inducible YAP1 S127A-driven rhabdomyosarcoma (RMS) tumors, control skeletal muscle and regressed tumors following YAP1 normalization by doxycycline withdrawal were compared to determine the YAP1-regulated gene expression profile relevant to RMS formation.
Publication Title
The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 17 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Selected soil-borne rhizobacteria can trigger an induced systemic resistance (ISR) that is effective against a broad spectrum of pathogens. In Arabidopsis thaliana, the root-specific transcription factor MYB72 is required for the onset of ISR, but is also associated with plant survival under conditions of iron deficiency. Here we investigated the role of MYB72 in both processes. To identify MYB72 target genes, we analyzed the root transcriptomes of wild-type Col-0, mutant myb72, and complemented 35S:FLAG-MYB72/myb72 plants in response to ISR-inducing Pseudomonas fluorescens WCS417. Five WCS417-inducible genes were misregulated in myb72 and complemented in 35S:FLAG-MYB72/myb72. Amongst these, we uncovered -glucosidase BGLU42 as a novel component of the ISR signaling pathway. Overexpression of BGLU42 resulted in constitutive disease resistance, whereas bglu42 was defective in ISR. Furthermore, we found 195 genes to be constitutively upregulated in MYB72-overexpressing roots in the absence of WCS417. Many of these encode enzymes involved in the production of iron-mobilizing phenolic metabolites under conditions of iron deficiency. We provide evidence that BGLU42 is required for their release into the rhizosphere. Together, this work highlights a thus far unidentified link between the ability of beneficial rhizobacteria to stimulate systemic immunity and mechanisms induced by iron deficiency in host plants.
Publication Title
β-Glucosidase BGLU42 is a MYB72-dependent key regulator of rhizobacteria-induced systemic resistance and modulates iron deficiency responses in Arabidopsis roots.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Argonaute (Ago) proteins mediate post-transcriptional gene repression by binding guide microRNAs (miRNAs) to regulate targeted RNAs. To confidently assess Agobound small RNAs, we adapted a mouse embryonic stem cell system to express a single inducible epitope-tagged Ago protein. Here, we report the small RNA profile of Agodeficient cells and determine Ago-dependent stability is a common feature of mammalian miRNAs. Considering both in vivo Ago-dependence for stability and Ago2 binding as defined by immunopurification, we have identified a novel class of non-canonical miRNAs derived from protein-coding gene promoters, which we name transcriptional start site miRNAs (TSS-miRNAs). A subset of promoter-proximal RNA polymerase II complexes produce hairpin RNAs that are processed in a DGCR8/Drosha-independent, but Dicer-dependent manner. TSS-miRNA activity is detectable endogenously, upon transfection of a mimic or by mRNA overexpression. Finally, we present evidence of differential expression and conservation in humans, suggesting important roles in gene regulation. Overall design: Examination of Ago immunoprecipitations and mESC without Ago proteins
Publication Title
Argonaute-bound small RNAs from promoter-proximal RNA polymerase II.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Target competition (ceRNA crosstalk) within miRNA-regulated gene networks has been proposed to influence biological systems. To assess target competition, we characterize and quantitate miRNA networks in two cell types. Argonaute iCLIP reveals that hierarchical binding of high to low affinity miRNA targets is a key characteristic of in vivo activity. Quantification of cellular miRNA and mRNA/ncRNA target pool levels indicates that miRNA-Target pool ratios and an affinity partitioned target pool accurately predict in vivo Ago binding profiles and miRNA susceptibility to target competition. Using single-cell reporters, we directly test predictions and estimate ~3,000 additional high affinity target sites can affect active miRNA families with low endogenous miRNA-Target ratios, such as miR-92/25. In contrast, the highly expressed miR-294 and let-7 families are not susceptible to increases of nearly 10,000 sites. These results show differential susceptibility based on endogenous miRNA-Target pool ratios and provide a physiological context for ceRNA competition in vivo. Overall design: mRNA seq from TT-FHAgo2 mouse embryonic stem cells or Meschencymal stem cells grown with 2.5 µg/mL Dox to express Ago2 or removed from doxycycline for 96h.
Publication Title
Endogenous miRNA and target concentrations determine susceptibility to potential ceRNA competition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated ordination of miRNA and mRNA expression profiles.
Sample Metadata Fields
Specimen part
View Samples