Establishing reliable biomarkers for assessing and validating clinical diagnosis at early prodromal stages of Parkinson’s disease is crucial for developing therapies to slow or halt disease progression. Here, we present the largest study to date using whole blood gene expression profiling from over 500 individuals to identify an 87-gene blood-based signature. Our gene signature effectively differentiates between idiopathic PD patients and controls in both a validation cohort and an independent test cohort, and further highlights mitochondrial metabolism and ubiquitination/proteasomal degradation as potential pathways disrupted in Parkinson’s disease.
Analysis of blood-based gene expression in idiopathic Parkinson disease.
Sex, Specimen part, Subject
View SamplesAnalysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
Specimen part
View SamplesSTEP (striatal-enriched tyrosine phosphatase) is a brain-specific phosphatase named for its robust expression in striatum. Brains from homozygous and heterozygous STEP knockout mice and wild-type littermates were harvested, and striatum microdissected. RNA was extracted and hybridized to Affymetrix 230_2 microarray chips.
Downstream effects of striatal-enriched protein tyrosine phosphatase reduction on RNA expression in vivo and in vitro.
Sex, Specimen part, Treatment
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Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis.
Age, Specimen part
View SamplesEvaluation of transcriptional changes in the striatum may be an effective approach to understanding the natural history of changes in expression contributing to the pathogenesis of Huntington disease (HD). We have performed genome-wide expression profiling of the YAC128 transgenic mouse model of HD at 12 and 24 months of age using two platforms in parallel; Affymetrix and Illumina. We performed gene expression profiling on the same striatal mRNA across both platforms.
Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis.
Age, Specimen part
View SamplesD-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion.
Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: changes in gene expression and associated regulatory networks resulting from serine deficiency.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Specimen part, Cell line
View SamplesTumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Specimen part
View SamplesTumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.
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