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E-MEXP-2127
Saccharomyces cerevisiae
6 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The use of yeast as a delivery system is an attractive option for the oral administration of therapeutic agents. We recently developed mutants of Saccharomyces cerevisiae capable of lysis upon conditional down-regulation of the expression of the cell wall genes PKC1 and SRB1. The lysis mechanism of the mutant is based on the use of the MET3 promoter, which, upon addition of methionine and cysteine, blocks transcription of SRB1 and PKC1. This strain has the potential to be an integral part of an oral yeast delivery system, in which there is lysis of yeasts in the human gut, followed by release of recombinant proteins for therapeutic use. In order to provide proof-of-principle, the system was evaluated testing the cells viability and lysis performance under conditions, which simulate those found in the human stomach and the duodenum. Upon incubation of yeast cells in these conditions, lysis could be induced and was accompanied by release of GFP reporter protein into the medium. However, the conditional lysis mechanism based on the MET3 promoter is not applicable in vivo. Therefore, alternative promoters suitable for in-vivo down-regulation of SRB1 and PKC1 were identified by a microarray experiments. The transcripts of genes ANB1, TIR1, and MF(ALPHA)2 were significantly reduced upon exposure of the yeast cells to conditions of the two gut compartments. Their promoters could be used to down-regulate SRB1/VIG9 and PKC1 in vivo to achieve lysis of the yeast in the gut to release cargo therapeutic proteins.
Publication Title
Conditional cell-wall mutants of Saccharomyces cerevisiae as delivery vehicles for therapeutic agents in vivo to the GI tract.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Lamin A/C was ablated in pancreatic acinar cells using Elastase1 driven, Cre-ErT mediated, LoxP recombination, causing excision of exons 10 and 11 of the Lmna gene
Publication Title
Lamin A/C Maintains Exocrine Pancreas Homeostasis by Regulating Stability of RB and Activity of E2F.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Epidemiologic and animal studies implicate overconsumption of fructose in the development of non-alcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remains largely unknown. We present evidence supporting the essential function of the lipogenic transcription factor ChREBP in mediating adaptation response to fructose and protecting against fructose-induced hepatotoxicity. High-fructose diet (HFrD) activates hepatic lipogenesis via a ChREBP-dependent manner in wildtype mice, while inducing steatohepatitis in Chrebp-KO mice. In Chrebp-KO mouse livers, HFrD reduces levels of molecular chaperones and activates the CHOP-dependent unfolded protein response, whereas administration of chemical chaperone or Chop shRNA rescues liver injury. Gene expression profiling revealed elevated expression of cholesterol biosynthesis genes in Chrebp-KO livers after HFrD, in parallel with increased abundance of nuclear SREBP2.
Publication Title
Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 43 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 43 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparison of Foxl2-null ovaries to wildtype ovaries, ovaries lacking Wnt4 or Kit, or testes, throughout mouse development.
Publication Title
Foxl2 functions in sex determination and histogenesis throughout mouse ovary development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 114 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.
Publication Title
Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.
Sample Metadata Fields
Disease stage
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- (lluminamouse6v1.1expressionbeadchip[arrayaddressidversion), Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Sample Metadata Fields
Sex, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
(lluminamouse6v1.1expressionbeadchip[arrayaddressidversion)
Description
U3A cells stably expressing wild-type STAT1 or STAT1-CC were treated with interferon beta (10U/ml) or control for 24 hours to assess effects of stat1 modifications, interferon, and the interaction on gene expression.
Publication Title
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Induced pluripotent stem cells hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained.
Publication Title
Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 21 Downloadable Samples
Illumina HiSeq 2500
Description
Somatic cancer driver mutations may result in distinctly diverging phenotypic outputs. Thus, a common driver lesion may result in cancer subtypes with distinct clinical presentations and outcomes. The diverging phenotypic outputs of mutations result from the superimposition of the mutations with distinct progenitor cell populations that have differing lineage potential. However, our ability to test this hypothesis has been challenged by currently available tools. For example, flow cytometry is limited in its inability to resolve lineage commitment of early progenitors. Single-cell RNA sequencing (scRNA-seq) may provide higher resolution mapping of the early progenitor populations as long as high throughput technology is available to sequence thousands of single cells. Nevertheless, high throughput scRNA-seq is limited in its inability to jointly and robustly detect the mutational status and the transcriptional profile from the same cell. To overcome these limitations, we propose the use of scRNA-seq combined with targeted mutation sequencing from transcrptional read-outs. Overall design: We apply this method to study myeloid neopasms, in which the comlex process of hematopoiesis is corrupted by mutated stem and progenitor cells.
Publication Title
Somatic mutations and cell identity linked by Genotyping of Transcriptomes.
Sample Metadata Fields
Sex, Age, Disease, Treatment, Subject
View Samples