The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing kidney. The central thesis is straightforward. The combination of fluorescent activated cell sorting (FACS) plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing kidney. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene in FACS isolated components of the developing kidney. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone.
Gene expression programs of mouse endothelial cells in kidney development and disease.
Sex
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.
Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment.
Sex
View SamplesKnockdown of the transcription factor PU.1 (Spi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of PU.1 knockdown hematopoietic stem cells (HSC) in the preleukemic phase by linear amplification and genome-wide array analysis to identify transcriptional changes preceding malignant transformation. Hierarchical cluster analysis and principal component analysis clearly distinguished PU.1 knockdown from wildtype HSC. Jun family transcription factors c-Jun and JunB were among the top downregulated targets. Retroviral restoration of c-Jun expression in bone marrow cells of preleukemic mice partially rescued the PU.1-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to reduced clonogenic growth, loss of leukemic self-renewal capacity, and prevented leukemia in transplanted NOD-SCID mice. Examination of 305 AML patients confirmed the correlation between PU.1 and JunB downregulation and suggests its relevance in human disease. These results delineate a transcriptional pattern that precedes the leukemic transformation in PU.1 knockdown HSC and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1-induced AML by blocking differentiation (c-Jun) and increasing self-renewal (JunB). Therefore, examination of disturbed gene expression in HSC can identify genes whose dysregulation is essential for leukemic stem cell function and are targets for therapeutic interventions.
Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells.
No sample metadata fields
View SamplesWe use the zebrafish embryo model to study the innate immune response against polystyrene particles. Therefore, we injected 700nm polystyrene into the yolk at 2 dpf and took samples at 1 and 3 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by polystyrene particle toxicity. RNA was isolated from embryos at 1 and 3 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (2dpf) with 1nl of 5mg/ml of 700nm red fluorescent polystyrene particles suspended in PVP (Polyvinylpyrrolidone) (n=3), mock injected with pvp (n=2), or Non-injected as a control (n=3). After injections embryos were transferred into fresh egg water and incubated at 28°C. At 1 and 3 days post injection 10 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Pathway analysis of systemic transcriptome responses to injected polystyrene particles in zebrafish larvae.
No sample metadata fields
View SamplesThe molecular targets of SRC-2 regulation in the murine liver stimulate fatty acid degradation and glycolytic pathway while fatty acid, cholesterol, and steroid biosynthetic pathways are down-regulated.
The genomic analysis of the impact of steroid receptor coactivators ablation on hepatic metabolism.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Specimen part, Cell line
View SamplesIkaros family DNA binding proteins are critical regulators of B cell development. To identify Ikaros-regulated genes in pre-B cells we performed gene expression studies at enhanced temporal resolution.
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Specimen part, Cell line
View SamplesNeurofibromatosis Type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating effects of hyperactive Ras in NF1 tumors are unknown. Cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs identified global negative feedback of genes that regulate Ras-Raf- MEK- extracellular signal-regulated protein kinase (ERK) signaling in both species. Nonetheless, activation of ERK was sustained in mouse and human neurofibromas and MPNST. PD0325901, a highly selective pharmacological inhibitor of MEK, was used to test whether sustained Ras-Raf-MEK-ERK signaling contributes to neurofibroma growth in the Nf1fl/fl;Dhh-cre mouse model or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in >80% of mice tested. PD0325901 also caused effects on tumor vasculature. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide strong rationale for testing MEK inhibitors in NF1 clinical trials.
MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.
Specimen part
View SamplesTriggering of B cell receptors (BCR) induces a massive synthesis of NFATc1 in splenic B cells. By inactivating the Nfatc1 gene and re-expressing NFATc1 we show that NFATc1 levels are critical for the survival of splenic B cells upon BCR stimulation. NFATc1 ablation led to decreased BCR-induced Ca++ flux and proliferation of splenic B cells, increased apoptosis and suppressed germinal centre formation and immunoglobulin class switch by T cell-independent antigens. By controlling IL-10 synthesis in B cells, NFATc1 supported the proliferation and IL-2 synthesis of T cells in vitro and appeared to contribute to the mild clinical course of Experimental Autoimmune Encephalomyelitis in mice bearing NFATc1-/- B cells. These data indicate NFATc1 as a key factor controlling B cell function.
NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
Specimen part
View SamplesIn this dataset, we include the expression data obtained from KRas expressing tumors, matched Kras expressing tumor spheres, surviving cells and surviving cells after KRas re-expression for 24hs
Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function.
Specimen part
View Samples