Propose: We used next-generation RNA sequencing (RNA-seq) to characterize the transcriptional changes in primary human melanocytes during recessive Cole disease. Our patient carried missense mutation in the ENPP1 gene (c.358T>C; p.C120R). RNA-seq was performed using mRNA extracted from primary hypo- and hyper-pigmented melanocytes isolated from affected patient and melanocytes from his healthy heterozygous sibling and an aged- and ethnicity-matched control. Results: A pairwise fold-change comparison was performed and genes were computationally filtered using a cutoff of more than 2 fold change and P<0.01. We first compared hyper-pigmented melanocytes to each control individually and then overlapped the results to obtain a list of 1041 up-regulated and 692 down-regulated genes. The same analysis was done for hypo-pigmented melanocytes to found that 535 genes were up-regulated and 520 were down-regulated. Finally, to obtain a profile of the overall differential gene expression, down-regulated genes in hyper and hypo-pigmented cells were overlapped to identify 143 genes that were down-regulated in patient melanocytes compared to controls regardless of pigmentation status. Similar analysis was performed to obtain the list of 172 up-regulated genes. We selected 36 deregulated genes, most of which were associated with melanocyte development and pigmentation signaling pathways, and validated 32 of them by Q-PCR, indicating that our RNA-Seq data was accurate and reliable. Conclusion: Our study represents the first analysis of hypo- and hyper-pigmented primary melanocytes isolated from affected patient versus healthy controls in recessive Cole disese pathology. Overall design: mRNA profiles of hyper- and hypo-pigmented mutant melanocytes, heterozygous and wild type melanocytes were sequenced in triplicate on the Hiseq 2500 High output 100PE
ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.
Sex, Age, Specimen part, Subject
View SamplesThe insulin-like growth factor-I (IGF-IR) and androgen (AR) receptors are important players in prostate cancer biology. Functional interactions between the IGF-I and androgen signaling pathways seem to have crucial roles in the progression of prostate cancer from early (benign) to advanced (metastatic) stages. DNA methylation is a major epigenetic alteration affecting gene expression. Hypermethylation of tumor suppressor promoters is a frequent event in human cancer, leading to inactivation and repression of specific genes. The aim of the present study was to identify the entire set of methylated genes (methylome) in a cellular model that replicates prostate cancer progression.
Global methylation analysis identifies PITX2 as an upstream regulator of the androgen receptor and IGF-I receptor genes in prostate cancer.
Cell line, Treatment, Time
View SamplesThere is much controversy about the role of T-regulatory cells (Treg) in human colon cancer. High densities of tumor-infiltrating Treg can correlate with better or worse clinical outcomes depending on the sutdy. Treg have potent anti-inflammatory functions that have been shown to control cancer progression. However, Treg isolated from patient with colon cancer or in mouse models of polyposis do not have the ability to suppress inflammation and instead promote cancer. Gene expression was preformed to determine differences between Treg isolated from healthy mice and Treg isolated from polyp-ridden mice.
Expression of RORγt marks a pathogenic regulatory T cell subset in human colon cancer.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesWe introduced the HCMV IE1 gene into a mouse model of spontaneous glioma driven by p53KD and overexpression of Ras and PDGF and compared the transcriptomes of mouse gliomas +/- IE1. The following plasmids were utilized for glioma induction in equal parts: pT2/C-Luc/PGK-SB100, pT2/Cag-NrasV12, pT2/shP53/GFP4/mPDGF, and pT2/Cag-IE1 or pT2/C-Neo.
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesHuman ESCs are pluripotent cells that have the capacity of self renewal for a prolonged period in vitro, and can differentiate into derivatives of all three primary germ layers: endoderm, mesoderm and ectoderm. Human ESCs are responsive to a wide range of factors in vitro that can direct their differentiation into specific cell types. We analyzed the effect of nicotinamide (NIC) on differentiation of hESCs in vitro. CEL file for GSM424319 is unavailable.
Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells.
Specimen part, Treatment
View SamplesPrimary human GBM stem like cells were infected with HCMV TR strain (MOI=1) and treated with IE siRNA (a combination of oligos targeting IE1 and IE2 HCMV genes)
Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.
Specimen part
View SamplesTo understand the link between invasion behavior and the steps of metastasis formation, we isolated invasive subpopulations from MDA-MB-231 cells in vitro using matrigel coated boyden chambers. Whole genome transcriptional profiling was used to characterize the expression changes uniquely related to invasive abilities of these cells.
Invading basement membrane matrix is sufficient for MDA-MB-231 breast cancer cells to develop a stable in vivo metastatic phenotype.
Cell line
View SamplesSenescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to nave normal cells. We define this phenomenon as paracrine senescence
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
Specimen part, Cell line
View SamplesIn this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.
A peripheral blood diagnostic test for acute rejection in renal transplantation.
Disease, Disease stage
View Samples