During mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling.
Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks.
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View SamplesSuppressor of cytokine signaling 3 (SOCS3) down-regulates several signaling pathways in multiple cell types, and previous data suggest that SOCS3 may shut off cytokine activation at the early stages of liver regeneration. We developed hepatocyte-specific Socs3 knockout (Socs3 h-KO) mice to directly study the role of SOCS3 during liver regeneration after 2/3 partial hepatectomy (PH). Socs3 h-KO mice demonstrate marked enhancement of DNA replication and liver weight restoration after 2/3 PH in comparison with littermate controls. Without SOCS3, signal transducer and activator of transcription 3 (STAT3) phosphorylation is prolonged, and activation of the mitogenic kinases extracellular signal-regulated kinase 1/2 (ERK1/2) is enhanced after PH. In vitro, we show that SOCS3 deficiency enhances hepatocyte proliferation in association with enhanced STAT3 and ERK activation after epidermal growth factor (EGF) or interleukin 6 (IL-6) stimulation. Microarray analyses show that SOCS3 modulates a distinct set of genes after PH, which fall into diverse physiologic categories. Using a model of chemical-induced carcinogenesis, we found that Socs3 h-KO mice develop hepatocellular carcinoma (HCC) at an accelerated rate. By acting on cytokines and multiple proliferative pathways, SOCS3 modulates both physiologic and neoplastic proliferative processes in the liver, and may act as a tumor suppressor.
Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3.
No sample metadata fields
View SamplesTo assess in vitro derived podocytes, we examined the transcriptional changes during human podocyte development and applied that knowledge to pinpoint strengths and limitations of hESC-derived podocytes. Overall design: We performed transcriptionaling profiling of kidney organoids and organoid-derived MAFB-eGFP+ podocytes at various differentiation time points.
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Subject
View SamplesIn order to characterize and benchmark the podocytes-like cells generated through human ES cell differentiation, we generated transcriptional profiles of renal corpuscles from embryonic human kidneys using RNA-Seq. To compare, we also performed RNA-Seq of human immortalized podocyte cell lines before and after thermoswitch. Overall design: We performed RNA-Seq of poly-A selected RNA from hESC-derived kidney organoids, organoid-derived MAFB-eGFP+ podocytes at different time points, and human immortalized podocytes.
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Specimen part, Subject
View SamplesAcute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.
Sex, Specimen part, Race
View SamplesWomen suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. This study used a mouse model to dissociate these factors and found no differences in peripheral afferent neurons or in the spinal cord immune response to neuropathic injury. However, it did identify potential sexual dimorphisms in peripheral adaptive immune responses. Overall design: RNA-seq of naïve FACS-purified DRG neurons and MACS-purified DRG neurons after partial sciatic nerve ligation (day 8): comparison of male versus female samples
Sex differences in peripheral not central immune responses to pain-inducing injury.
Sex, Specimen part, Cell line, Subject
View SamplesOur laboratory's interest is in understanding the molecular principles that underlie the regional organization of the mammalian metanephric kidney. Our goal is to generate a detailed spatial map of the cellular expression of selected regulatory genes during mammalian kidney development. The goal of this study is to identify a population of genes that are enriched in the renal vesicle (RV) and its derivatives using Wnt4 mutants.
Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation.
Sex
View SamplesRenal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Alteration of human blood cell transcriptome in uremia.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesAcute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity.
Specimen part, Cell line
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