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SRP034552
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors ß-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of ß-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds ß-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation. Overall design: RNA-Seq analyses was used to characterize gene expression in primary myoblasts from wild-type and Barx2 knockout mice.
Publication Title
Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 89 Downloadable Samples
- Illumina HiSeq 2500
Description
We developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof-of-principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both shRNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons. Overall design: We tried to idenitify transcripitional profiles and specific transcription factors that involved in of different stages during hypothalamic neuron differentiation from single cell sequencing for hESC-derived Day27 hypothalamic neurons, Day 12 neuron progenitors and undifferentiated stem cells
Publication Title
PC1/3 Deficiency Impacts Pro-opiomelanocortin Processing in Human Embryonic Stem Cell-Derived Hypothalamic Neurons.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- IlluminaHiSeq2500
Description
We characterized the gene expression by Hierarchical Clustering and one-matrix clustering in hESC, day 12 progenitors, day 25-day 27, day82 differentiated hypothalamic neurons from hESCs and day 45 neurons derived from iPSCs generated from controls (2 independent) and BBS (Bardet-Biedl Syndrome, 3 independent) subjects. Overall design: RNA was isolated from cells of 13 samples (1 hESC, triplicate for day 12 progenitors, 1 day 25 neuron sample, duplicate for day 27 neuron samples, 1 day 82 neuron sample, five day 45 neuron samples made from 5 independent iPSC lines ) using RNeasy Micro Kit (QIAGEN). Quality control of the RNA was carried out with the Agilent Bio-analyzer, Qubit 2.0 at the MPSR of Columbia University. 100 ng of RNA with RIN = 9 were used for generating mRNA-focused libraries using TruSeq RNA Sample Preparation Kit v2 and sequencing on an Illumina 2000/2500 V3 Instrument offered by the Columbia Genome Center.
Publication Title
Differentiation of hypothalamic-like neurons from human pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 70 Downloadable Samples
- Illumina HiSeq 2000
Description
We applied Next-Generation Sequencing (NGS) to miRNAs from blood samples of 48 AD (Alzheimer''s Disease) patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression level. Of these, 82 were higher and 58 lower abundant in samples from AD patients. We selected a panel of 12 miRNAs for a qRT-PCR analysis on a larger cohort of 202 samples including not only AD patients and healthy controls but also patients with other CNS illnesses: Multiple Sclerosis, Parkinson''s Disease, Major Depression, Bipolar Disorder, Schizophrenia, and Mild Cognitive Impairment, which is assumed to represent a transitional period before the development of AD. MiRNA target enrichment analysis of the selected 12 miRNAs indicated an involvement of miRNAs in nervous system development, neuron projection, neuron projection development, and neuron projection morphogenesis, respectively. Using this 12-miRNA signature we were able to differentiate between AD and controls with an accuracy of 93.3%, a specificity of 95.1%, and a sensitivity of 91.5%. The differentiation of AD from other neurological diseases was possible with accuracies between 73.8% and 77.8%. The differentiation of the other CNS disorders from controls yielded even higher accuracies. Overall design: Examination of the miRNA profile in blood samples of 48 AD patients and 22 controls
Publication Title
A blood based 12-miRNA signature of Alzheimer disease patients.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPAR target genes. The aim of this study was to investigate the role of PPAR in heme-induced hyperproliferation and hyperplasia. Male PPAR KO and WT mice received a purified diet with or without heme. As PPAR is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPAR leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPAR in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPAR KO mice. We conclude that PPAR plays a protective role in colon against oxidative stress, but PPAR does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia.
Publication Title
Dietary heme-mediated PPARα activation does not affect the heme-induced epithelial hyperproliferation and hyperplasia in mouse colon.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Differential gene expression analysis were performed between Pitx1 silenced SCC cells and controls in two independent SCC lines Overall design: Compared control and Pitx1 deficient cells to define gene sets control by Pitx1 in SCCs.
Publication Title
De Novo PITX1 Expression Controls Bi-Stable Transcriptional Circuits to Govern Self-Renewal and Differentiation in Squamous Cell Carcinoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 49 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 39 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB).
Publication Title
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We performed gene expression profile of different B cell populations found in old (18 months old) C57BL/6 female mouse (B1 cells were recovered from both young and old C57BL/6 mice). Mice were nave and healthy (no autoimmunity was detected at the time of the experiment).
Publication Title
Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c⁺ B-cell population is important for the development of autoimmunity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
29-32 days old male mice where either treated with Phenobarbital or untreated
Publication Title
Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples