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SRP131070
Arabidopsis thaliana
12 Downloadable Samples
Illumina Genome Analyzer IIx
Description
3 weeks old aseptically grown WT and loss-of-function lines of SnRK1s (transgenic SnRK1a1 T-DNA insertion mutant line crossed with an estradiol inducible amiRNA construct targeting SnRK1a2) and group S1 bZIPs (bZIP1/bZIP53 T-DNA insertion mutant line crossed with an estradiol inducible amiRNA construct simultaneously targeting bZIP2, bZIP11 and bZIP44) were cultivated for 6h under extended night. Total RNA was extracted from whole seedlings and used for RNAseq library preparation. Overall design: Examination of global transcriptional changes in WT as well as SnRK1 and S1-bZIP knockdown lines in response to short-term dark cultivation.
Publication Title
Snf1-RELATED KINASE1-Controlled C/S<sub>1</sub>-bZIP Signaling Activates Alternative Mitochondrial Metabolic Pathways to Ensure Plant Survival in Extended Darkness.
Sample Metadata Fields
Age, Subject
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Soil salinity increasingly causes crop losses worldwide. Although roots are the primary targets of salt stress, the signaling networks that facilitate metabolic reprogramming to induce stress tolerance are less understood than those in leaves. Here, a combination of transcriptomic and metabolic approaches was performed in salt-treated Arabidopsis thaliana roots, which revealed that the group S1 basic leucine zipper transcription factors bZIP1 and bZIP53 reprogram primary C- and N-metabolism. In particular, gluconeogenesis and amino acid catabolism are affected by these transcription factors. Importantly, bZIP1 expression reflects cellular stress and energy status in roots. In addition to the well-described abiotic stress response pathway initiated by the hormone abscisic acid (ABA) and executed by SnRK2 (Snf1-RELATED-PROTEIN-KINASE2) and AREB-like bZIP factors, we identify a structurally related ABA-independent signaling module consisting of SnRK1s and S1 bZIPs. Crosstalk between these signaling pathways recruits particular bZIP factor combinations to establish at least four distinct gene expression patterns. Understanding this signaling network provides a framework for securing future crop productivity.
Publication Title
Crosstalk between Two bZIP Signaling Pathways Orchestrates Salt-Induced Metabolic Reprogramming in Arabidopsis Roots.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Schizophrenia (SZ) and autism spectrum disorders (ASD) are highly heritable neuropsychiatric/neurodevelopmental disorders, although environmental factors, such as maternal immune activation (MIA), play a role as well. Inflammatory cytokines appear to mediate the effects of MIA on neurogenesis and behavior in animal models. However, drugs and cytokines that trigger MIA can also induce a febrile reaction, which could have independent effects on neurogenesis through heat shock (HS)-regulated cellular stress pathways. However, this has not been well-studied. As a first step towards addressing the role of fever in MIA, we used a recently described model of human brain development in which induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional neuronal aggregates that resemble a first trimester telencephalon. RNA-seq was carried out on aggregates that were heat shocked at 39oC for 24 hours, along with their control partners maintained at 37oC. Overall, 186 genes showed significant differences in expression following HS (p<0.05), including known HS-inducible genes, as expected, as well as those coding for NGFR and a number of SZ and ASD candidates, including SMARCA2, DPP10, ARNT2, AHI1 and ZNF804A. The degree to which the expression of these genes decrease or increase during HS is similar to that found in copy loss and copy gain CNVs, although the effects of HS are likely to be more transient. Overall design: RNA-seq was carried out on neuronal aggregates as described by Mariani et al. with slight modification (PMID:22761314). For the heat shock experiment, a group of 49 day old aggregates was placed in an incubator set at 39C for 24 hours, while control sets of aggregates were maintained at 37C. The incubator conditions were otherwise unchanged. After detaching the aggregates, total cellular RNA was isolated using the miRNeasy Kit (Qiagen) according to the manufacturer's protocol. Lastly, RNAseq profiles of HS and Control were compared
Publication Title
Heat shock alters the expression of schizophrenia and autism candidate genes in an induced pluripotent stem cell model of the human telencephalon.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 2500
Description
The rising prevalence of obesity and its associated metabolic abnormalities have become global diseases that carry considerable morbidity and mortality. While there is certainly an important genetic component, extensive human epidemiologic and animal model data suggest an epigenetic component to obesity. Nevertheless, the cellular and molecular underpinnings of these pathways and how they contribute to the development of obesity remain to be elucidated. Suv420h1 and h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex-vivo and in vitro studies, we found that Suv420h1 and h2 respond to environmental stimuli and regulate metabolism by downregulating PPAR-?, a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-? target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulator of PPAR-? and the pathways controlling metabolism and weight balance in response to environmental stimuli. Overall design: For experiment 1, total RNA was isolated from males and females control- and Suv420h dKO-derived BAT. For experiment 2, total RNA was isolated from BAT collected from females control and Suv420h dKO mice after both diet regimes (nd = normal diet, hfd = high fat diet).
Publication Title
The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- IlluminaHiSeq2000
Description
Deletions at 15q11.2 have been established to increase risk for multiple neurodevelopmental disorders (NDDs) including schizophrenia and epilepsy, yet show variable expressivity between individuals. To investigate the potential role of CYFIP1, a gene within the locus, we carried out knockdown experiments in human neural progenitor cells derived from 15q11.2 neutral induced pluripotent stem cells. Transcriptional profiling and cellular assays support a prominent role for CYFIP1 in cytoskeletal remodeling across all lines examined. Validating the utility of this model for study of disease, genes implicated in schizophrenia and epilepsy but not other disorders or traits unrelated to the deletion, were enriched among mRNAs dysregulated following knockdown. Importantly, and consistent with the variable expressivity of 15q11.2 deletions, the magnitude of disease-related effects varied between donor lines. Towards mechanisms, FMRP targets and synaptic genes were overrepresented among dysregulated mRNAs and as such may contribute to the schizophrenia and epilepsy effects we observe. Further model validation, and new candidate epilepsy genes, comes from machine-learning analyses showing a striking similarity between a subset of dysregulated transcripts and well-established epilepsy genes. Results provide support for an important contribution of CYFIP1 in 15q11.2 mediated risk for NDDs and demonstrate that disease-related biological signatures are evident prior to neuronal differentiation. This new human model of disease will be useful in identifying compounds that could ameliorate outcomes in deletion carriers. Overall design: Investigation of CYFIP1 shRNA knockdown in three neural progenitor cell lines derived from induced pluripotent stem cells (3 control samples and 3 knockdown samples analyzed in each line)
Publication Title
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
The goal of this project is to study transcriptome change by knocking down ZNF804A, a schizophrenia and bipolar disorder candidate gene, in early neurons derived from iPSCs. Overall design: Neural progenitor cells (NPCs) were developed from human induced pluripotent stem cells (iPSCs) and transduced by two independent shRNA vectors targeting ZNF804A, a schizophrenia and bipolar disorder candidate gene. After recovery and selection in puromycin, neuronal differentiation was induced. After 14 days, RNA was recovered and analyzed by RNA-seq. The expression profiles were compared with NPCs that were transduced with scrambled control vectors. This corresponds to controls 1-3 and KD 1-3, which was carried out on a male iPSC line. Scramble 1 and 2 and KD1 and 2 are technical replicates. Scrambled 3 and KD 3 were carried out on an independent NPC culture. For control 4 and KD4, neuronal differentiation was induced, and on day 10 the cells were transduced with the same ZNF804A KD and scrambled control vectors used for scrambled control 3 and KD3. In addition, this last set was carried out on a female iPSC line
Publication Title
ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Molecular definition of human extraocular muscles (EOM). Human EOM were compared with limb (quadriceps femoris) muscle.
Publication Title
Definition of the unique human extraocular muscle allotype by expression profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
Publication Title
Expression profiling reveals metabolic and structural components of extraocular muscles.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Induced pluripotent stem cell (iPSC) technology has the potential to address the inaccessibility of the human brain by providing investigators with patient-specific neurons that can potentially be used to carry out molecular, electrophysiological and pharmacological studies {{855 Takahashi,K. 2006}}. Although iPSC technology was primarily conceived and developed as a means to bypass the use of human embryonic stem cells (hESCs) for regenerative medicine, its potential for disease modeling may prove to be equally valuable, especially for neuropsychiatric disorders.
Publication Title
Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Maternal obesity is linked with increased adverse outcomes for mother and fetus. However, the metabolic impact of excessive fat accumulation within the altered hormonal context of pregnancy is not well understood. We used a murine model of obesity, the high fat diet-fed C57BL/6J mouse to determine adipose tissue-mediated molecular mechanisms driving metabolic dysfunction throughout pregnancy. Remarkably, obese mice exhibited a normalization of visceral fat accumulation at late-stage pregnancy (-53%, P<0.001 E18.5) to achieve levels comparable in mass (per gram of body weight) to that of non pregnant, control diet fed mice. Moreover, whilst obese pregnant mice showed a marked glucose intolerance and apparent insulin resistance at mid-stage pregnancy (E14.5), glucose homeostasis converged with that of lean pregnant mice at late-stage pregnancy, suggesting an unexpected amelioration of the worsening metabolic dysfunction in obese pregnant mice.
Publication Title
Pregnancy in obese mice protects selectively against visceral adiposity and is associated with increased adipocyte estrogen signalling.
Sample Metadata Fields
Specimen part
View Samples