This SuperSeries is composed of the SubSeries listed below.
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Time
View SamplesThe progression from stem cell to differentiated neuron is associated with extensive chromatin remodeling that controls gene expression, but the mechanisms that connect chromatin to gene expression are not well defined. Here we show that mutation of ZNF335 causes severe human microcephaly ("small brain"), small somatic size, and neonatal death. Germline Znf335 null mutations are embryonically lethal in mice, whereas RNA-interference studies and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. Znf335 is a component of a vertebrate-specific, trithorax H3K4 methylation complex, while global ChIP-seq and mRNA expression studies show that Znf335 is a previously unsuspected, direct regulator of REST/NRSF, a master regulator of neural gene expression and neural cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct evidence that this pathway regulates human neurogenesis and neuronal differentiation.
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Time
View SamplesWe measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA.
Common genetic mechanisms of blood pressure elevation in two independent rodent models of human essential hypertension.
No sample metadata fields
View SamplesWe performed Affymetrix MG-U74Av2 GeneChip experiements on mRNA from the adrenal glands of the BPH hypertensive and BPL hypotensive mouse strains. All mice were aged-matched at 5 weeks. We obtained the mice from Jackson Laboratories, Bar Harbor, ME.
Neuroendocrine transcriptome in genetic hypertension: multiple changes in diverse adrenal physiological systems.
No sample metadata fields
View SamplesRecent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance. Overall design: RNA-Seq of laser microdissection of motor neuron bodies from two biological replicates each of SOD1 YFP (wildtype 592) and SOD1 G85R YFP (737) transgenic mice.
RNA-Seq profiling of spinal cord motor neurons from a presymptomatic SOD1 ALS mouse.
Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A large gene network in immature erythroid cells is controlled by the myeloid and B cell transcriptional regulator PU.1.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Treatment
View SamplesInvasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Treatment
View SamplesWe compared the transcriptomes of ES cell derived erythroid progentor cells (ES-EP) and murine erythroleukemia (MEL) cells stably transfected with Gata-1 fused to ER.
A large gene network in immature erythroid cells is controlled by the myeloid and B cell transcriptional regulator PU.1.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View Samples