Renal cell carcinoma (RCC) is among the ten most common malignancies. By far, the most common histology is clear cell (ccRCC). The Cancer Genome Atlas and other large scale sequencing studies of ccRCC have been integral to the current understanding of molecular events underlying RCC and its biology. However, these data sets have focused on primary RCC which often demonstrates indolent behavior. In contrast, metastatic disease is the major cause of mortality associated with ccRCC. However, data sets examining metastatic tumor are sparse. We therefore undertook an integrative analysis of gene expression and DNA methylome profiling of metastatic ccRCC in addition to primary RCC and normal kidney. Integrative analysis of the methylome and transcriptome identified over 30 RCC specific genes whose mRNA expression inversely correlated with promoter methylation including several known targets of hypoxia inducible factors (HIFs). Notably, genes encoding several metabolism-related proteins were identified as differentially regulated via methylation. Collectively, our data provide novel insight into biology of aggressive RCC. Furthermore, they demonstrate a clear role for epigenetics in the promotion of HIF signaling and invasive phenotypes in renal cancer.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Specimen part
View SamplesUnderstanding gene expression changes during transformation from normal tissue to primary RCC and then to metastasis is important. Such analysis is pivotal for undertanding biology in renal cancer and also to unearth novel gene targets.
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis.
Specimen part
View SamplesWe sequenced mRNA from FACS purified hair follicle bulge stem cells from 21 d old control and ILK-deficient mice, 3 biological replicates each Overall design: Examination of mRNA levels in control and ILK-deficient hair follicle bulge stem cells
Integrin-linked kinase regulates the niche of quiescent epidermal stem cells.
No sample metadata fields
View SamplesGene Expression in d5 wound-edge tissues of MFG-E8 WT and MFG-E8 KO mice
Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.
Specimen part
View SamplesGenome-wide alternative splice analysis of RNA from lupus and its severe form lupus nephritis
Genome-wide peripheral blood transcriptome analysis of Arab female lupus and lupus nephritis.
Sex, Specimen part, Disease stage
View SamplesWe performed single-cell mRNA-Seq on wild-type mouse keratinocytes co-cultured with keratinocytes in which beta-catenin was activated. We identified seven distinct cell states in cultures that had not been exposed to the beta-catenin stimulus. Using temporal single-cell analysis we reconstruct the cell fate changes induced by neighbor Wnt activation. Gene expression heterogeneity was reduced in neighboring cells and this effect was most dramatic for protein synthesis associated genes. The changes in gene expression were accompanied by a shift from a quiescent to a more proliferative stem cell state. By integrating imaging and reconstructed sequential gene expression changes during the state transition we identified transcription factors, including Smad4 and Bcl3, that were responsible for effecting the transition in a contact-dependent manner. Our data indicate that non cell autonomous Wnt/beta-catenin signaling decreases transcriptional heterogeneity and further our understanding of how epidermal Wnt signaling orchestrates regeneration and self-renewal. Overall design: Comparison of cells exposed to Wnt activated neighbors versus unactivated.
Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells.
Specimen part, Treatment, Subject
View SamplesAirway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using exon microarrays and RNAsequencing. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. In conclusion, In vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium. Overall design: A total of eight independent RNAseq experiments were conducted. Four RNAseq experiments (n = 2 unstimulated, n = 2 stimulated with flagellin) were performed using AECs grown in monolayer. Four RNAseq experiments (n =2 unstimulated, n = 2 stimulated with flagellin) were conducted using AECs grown in ALI cultures
Plasticity of airway epithelial cell transcriptome in response to flagellin.
No sample metadata fields
View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses.
A pathway-based analysis on the effects of obstructive sleep apnea in modulating visceral fat transcriptome.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Plasticity of airway epithelial cell transcriptome in response to flagellin.
Specimen part, Treatment
View SamplesAirway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using exon microarrays and RNAsequencing. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. In conclusion, In vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium.
Plasticity of airway epithelial cell transcriptome in response to flagellin.
Specimen part, Treatment
View Samples