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GSE106076
Homo sapiens
65 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The development of an effective therapy against tauopathies like Alzheimers disease (AD) and frontotemporal dementia (FTD) remains challenging, partly due to limited access to fresh brain tissue, the lack of translational in vitro disease models and the fact that underlying molecular pathways remain to be deciphered. Several genes play an important role in the pathogenesis of AD and FTD, one of them being the MAPT gene encoding the microtubule-associated protein tau. Over the past few years, it has been shown that induced pluripotent stem cells (iPSC) can be used to model various human disorders and can serve as translational in vitro tools. Therefore, we generated iPSC harboring the pathogenic FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17) associated mutations IVS10+16 with and without P301S in MAPT using Zinc Finger Nuclease technology. Whole transcriptome analysis of MAPT IVS10+16 neurons reveals neuronal subtype differences, reduced neural progenitor proliferation potential and aberrant WNT signaling. Notably, all phenotypes were recapitulated using patient-derived neurons. Finally, an additional P301S mutation causes an increased calcium bursting frequency, reduced lysosomal acidity and tau oligomerization.
Publication Title
Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Retinitis Pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the Mller glia, play in the progression of the disease. Here we define gene expression changes in Mller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knock-out (Rhod-ko) models. The RNA repertoire of 28 single MGCs was comprehensively profiled, and a comparison was made between MGC from wild type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. MGCs have been shown to respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of GFAP. In this data, many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune related response. It is noteworthy that a high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells, and/or inherent heterogeneity among MGCs.
Publication Title
Gene expression changes within Müller glial cells in retinitis pigmentosa.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Enriched tumor epithelium from 61 primary and metastasis tumor specimens was obtained by laser capture microdissection (LCM) as previously described (Boersma et al., 2007). In brief, frozen 8-m serial sections from OCT-preserved frozen tissues were prepared and mounted on plain, uncharged microscope slides. One Hematoxylin/eosin-stained section of each specimen was reviewed by a pathologist to confirm diagnosis and presence of tumor. The pathologist indicated which representative sections of the tumors should be microdissected. LCM was performed with the Pixcell II LCM system (Arcturus, Mountain View, CA). Total RNA was isolated using the PicoPure protocol (Arcturus, Mountain View, CA). The mRNA was amplified with two linear amplification steps by in vitro transcription using the MEGAscript T7 kit (Ambion, Austin, TX) followed by the labeling step using the BioArray HighYield RNA Transcript Labeling Kit T3 from Enzo Life Sciences (Farmingdale, NY). Labeled cRNA was hybridized onto Affymetix GeneChip HG-U133 Plus 2.0 Arrays.
Publication Title
Integrative genomic and transcriptomic characterization of matched primary and metastatic liver and colorectal carcinoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 488 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used Affymetrix microarray profiling to analyze gene expression patterns in healthy donor liver as well as tumor and paired non-tumor tissue of HCC patients.
Publication Title
A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The overexpression of transcription factors Oct4, Sox2, Klf4, and c-Myc reprograms a somatic nucleus to one that is transcriptionally and epigenetically indistinguishable from an embryonic stem (ES) cell. However, it is still unclear if transcription factors can completely convert the nucleus of a differentiated cell into that of a distantly related cell type such that it maintains complete transcriptional and epigenetic reprogramming in the absence of exogenous factor expression. To test this idea, we screened a library of doxycycline-inducible vectors encoding neural stem cell (NSC)-expressed genes and found that stable, self-maintaining NSC-like cells could be induced under defined growth conditions after transduction of transcription factors. These induced NSCs (iNSCs) were characterized in the absence of exogenous factor induction and were shown to be transcriptionally, epigenetically, and functionally similar to endogenous embryonic cortical NSCs. Importantly, iNSCs could be generated from multiple adult cell types including liver cells and B-cells with genetic rearrangements. Our results show that self-maintaining proliferative neural cells can be induced from non-ectodermal cells by expressing specific combinations of transcription factors.
Publication Title
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 2500, NextSeq 550
Description
Individuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells. Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. All lines maintained CFTR mRNA production and formation of tight junctions. CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not. Baseline expression of both cytokines was not different between the lines regardless of CFTR genotype. All lines responded to TNFa and IL1b by increasing IL6 and CXCL8 (IL8) mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines. Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFa, were compared for differential expression as a function of CFTR genotype. While some genes appeared to be differentially expressed simply because of CFTR's absence, others required stimulation for differences to be apparent. Together, these data suggest cells respond to CFTR's absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation. With regards to inflammation, these data suggest a model in which CFTR's absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation. Overall design: Compare cells with intact CFTR to cells lacking CFTR for overall gene expression under basal and TNFa-stimulated conditions
Publication Title
Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Diabetes and obesity are widespread diseases with signifciant socioeconomic implications. We used three different types of human adipose tissue (epigastric, visceral, and subcutaneous) in order to determine differences in global gene expression between these adipose depots in severely obese patients.
Publication Title
Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.
Sample Metadata Fields
Specimen part, Race
View Samples