Human umbilical vein endothelial cells (HUVECs) were incubated for 48 h after transfection of scrambled siRNA or siRNA targeting Jmjd6 .
Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1.
Specimen part, Treatment
View SamplesRetinitis 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.
Gene expression changes within Müller glial cells in retinitis pigmentosa.
Specimen part
View SamplesEnriched 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.
Integrative genomic and transcriptomic characterization of matched primary and metastatic liver and colorectal carcinoma.
Specimen part, Disease, Disease stage
View SamplesWe 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.
A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients.
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Specimen part
View SamplesThe 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.
Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
Specimen part
View SamplesIndividuals 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
Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks.
Specimen part, Treatment, Subject
View SamplesDiabetes 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.
Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.
Specimen part, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma.
Specimen part, Disease, Disease stage
View SamplesWe compared transcriptomic profiles of 23 ICC tumor specimens to hepatocellular carcinoma (HCC) specimens using Affymetrix mRNA array and the miRNA array platforms to search for unique gene signatures linked to patient prognosis.
Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma.
Specimen part, Disease, Disease stage
View Samples