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GSE94754
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease and a leading cause of liver transplantation in the United Sates. Hedgehog (Hh) signaling has been implicated in liver lipid metabolism and the early stages of NAFLD; however, its precise role remains unclear. We examined the prevalence of NAFLD in patients with overt or microform holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Hh signaling. To test the hypothesis that Hh signaling attenuation predisposes to liver steatosis, we subjected Gli2 heterozygous null (Gli2+/-) mice to two unique dietary models of fatty liver. Compared to the general population, the prevalence of NAFLD was significantly higher in the HPE cohort independent of obesity, especially among younger individuals. Gli2 heterozygosity caused increased weight gain and liver steatosis on a high fat diet, and increased liver steatosis in the absence of weight gain on a methionine and choline deficient diet. Increased liver steatosis in Gli2+/- mice was associated with decreased expression of pro-fibrotic and pro-inflammatory genes and increased expression of PPAR, a potent anti-fibrogenic and anti-inflammatory regulator. In addition, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2+/- mice. Our results indicate that germline mutations affecting Hh signaling predispose to NAFLD with reduced or absent fibrosis, and might increase the risk of hepatocellular carcinoma.
Publication Title
Human germline hedgehog pathway mutations predispose to fatty liver.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
ClC-2 is a broadly expressed Cl- channel of the CLC family of Cl- channels and transporters which is abundantly expressed in brain. Here it was proposed to participate in lowering the cytoplasmic Cl- concentration of neurons, a process that establishes an inhibitory response to the neurotransmitters GABA and glycine (Staley et al., 1996). Heterozygous mutations in CLCN2 (the gene encoding ClC-2) were recently reported in a few patients with three clinically distinct forms of epilepsy (Haug et al, 2003). However, the disruption of ClC-2 in mice (ClC-2 KO mouse) did not entail epilepsy (Bösl et al., 2001; Nehrke et al., 2002) but myelin vacuolation in fiber tracts of the central nervous system. We used a gene expression profiling of the ClC-2 KO mouse in brain to identify possible disease mechanism which cause the observed myelin phenotype. As these myelin vacuolation became apparent in the fiber tracts of ClC-2 KO cerebellum at P28 and increased with age, we analysed the cerebellum of ClC-2 KO mice at different postnatal ages, before (P14) and after (P35) the KO cerebellum has been affected by myelin vacuolation.
Publication Title
Leukoencephalopathy upon disruption of the chloride channel ClC-2.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
12-oxo-phytodienoic acid (OPDA) and phytoprostane A1 (PPA1) are cyclopentenone oxylipins that are formed via the enzymatic
Publication Title
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
12-Oxo-phytodienoic acid (OPDA) and several phytoprostanes are structurally related cyclopentenone oxylipins that can be formed via the enzymatic jasmonate pathway and a non-enzymatic, free radical-catalyzed pathway, respectively. To elucidate the biological activities of phytoprostanes in comparison to OPDA as well as the metabolism we performed genome-wide expression analysis.
Publication Title
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
To study the development and function of “natural-arising” T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3+ CD4+ Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) ß-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR ß-chain was able to provide stronger TCR signals. This TCR-ß–driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3- CD4+ T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells. Overall design: We performed RNA-Seq analysis to determine the transcriptional differences between monoclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.TCRab.FoxP3GFP.Rag-/- and compared it with polyclonal FoxP3GFP-positive and -negative CD4+ T cells from NOD.FoxP3GFP mice
Publication Title
Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Nonsyndromic clefts of the palate and/or lip are common birth defects arising in about 1/700 live births worldwide. They are caused by multiple genetic and environmental factors, can only be corrected surgically and require complex post-operative care that imposes significant burdens on individuals and society. Our understanding of the molecular networks that control palatogenesis has advanced through studies on mouse genetic models of cleft palate. In particular, the transcription factor Pax9 regulates palatogenesis through the Bmp, Fgf and Shh pathways in mice. But there is still much to learn about Pax9's relationship with other signaling pathways in this process. Expression analyses and unbiased gene expression profiling studies offer a molecular explanation for the resolution of palatal defects by showing that Wnt and Eda/Edar-related genes are expressed in normal palatal tissues and that the Wnt and Eda/Edar signaling pathway is downstream of Pax9 in palatogenesis. Overall design: E13.5 mouse embryos palate were micro-dissceted, control and mutant samples were seperated and individually lyzed for the RNA extraction.
Publication Title
Small-molecule Wnt agonists correct cleft palates in <i>Pax9</i> mutant mice <i>in utero</i>.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 2500
Description
Nonsyndromic clefts of the palate and/or lip are common birth defects arising in about 1/700 live births worldwide. They are caused by multiple genetic and environmental factors, can only be corrected surgically and require complex post-operative care that imposes significant burdens on individuals and society. Our understanding of the molecular networks that control palatogenesis has advanced through studies on mouse genetic models of cleft palate. In particular, the transcription factor Pax9 regulates palatogenesis through the Bmp, Fgf and Shh pathways in mice. But there is still much to learn about Pax9''s relationship with other signaling pathways in this process. Here we show alterations of Wnt expression and decreased Wnt activity in Pax9-/- palatal shelves are a likely result of Pax9''s ability to directly bind and repress the promoters of Dkk1 and Dkk2, proteins that antagonize Wnt signaling. We exploited this relationship by delivering small-molecule Dkk inhibitors into the tail-veins of pregnant Pax9+/- females from E10.5 to E14.5. Such therapies restored Wnt signaling, promoted cell proliferation, bone formation and fusion of palatal shelves in Pax9-/- embryos. These data uncover a connection between the roles of Pax9 and Wnt genes in palatogenesis and offer a new approach for treating human cleft palates. Overall design: E14 embryos of Pax9-/- and control littermates with or without WAY-262611 treatment, mouse embryos palate were micro-dissected, control and mutant samples were separated and individually lysed for the RNA extraction.
Publication Title
Small-molecule Wnt agonists correct cleft palates in <i>Pax9</i> mutant mice <i>in utero</i>.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- NextSeq 500
Description
Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Overall design: RNA-seq of myeloid progenitors and Ly6Chi monocytes from mouse bone marrow. 4 progenitor fractions (GMPs, MDPs, GPs and a mixed fraction of MPs + cMoPs) were isolated from the pooled bone marrow of 20 mice. GMPs and MDPs were also cultured in vitro and the monocyte-committed progenitors and Ly6Chi monocytes they produced were also harvested. RNA was extracted from the 4 ex vivo progenitor fractions, and the 4 populations derived in vitro (GMP-derived monocyte progenitors = MP; MDP-derived monocyte progenitors = cMoP; GMP-derived Ly6Chi monocytes = G-mono; MDP-derived Ly6Chi monocytes = M-mono). The whole process was repeated using 20 additional mice to obtain a replicate set of samples.
Publication Title
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Loss of Syk in normal breast cells in vivo and in vitro: gene expression and phenotypic switch to stem-cell like with induction of invadopodia
Publication Title
Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.
Sample Metadata Fields
Cell line
View Samples