Disruption of local iron homeostasis is a common feature of neurodegenerative diseases. We focused on dopaminergic neurons, asking how iron transport proteins modulate iron homeostasis in vivo. Inactivation of the transmembrane iron exporter ferroportin had no apparent consequences. However, loss of the transferrin receptor 1, involved in iron uptake, caused profound, age-progressive neurodegeneration with features similar to Parkinsons disease. There was gradual loss of dopaminergic projections in the striatum with subsequent death of dopaminergic neurons in the substantia nigra. After depletion of 30% of the neurons the mice developed neurobehavioral parkinsonism, with evidence of mitochondrial dysfunction and impaired mitochondrial autophagy. Molecular analysis revealed strong signatures indicative of attempted axonal regeneration, a metabolic switch to glycolysis and the unfolded protein response. We speculate that cellular iron deficiency may contribute to neurodegeneration in human patients
Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons.
Age, Specimen part
View SamplesThe nuclear hormone receptor, estrogen receptor-alpha (ER), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ER activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ER colocalization at chromatin binding sites across the genome of breast cancer cells.
Genomic collaboration of estrogen receptor alpha and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs.
Disease, Disease stage, Cell line, Time
View SamplesAcute myeloid leukemia (AML) is a complex, heterogeneous disease with variable outcomes following curative intent chemotherapy. AML with inv(3) is a genetic subgroup characterized by low response rate to induction type chemotherapy and hence is among the worst long term survivorship of the AMLs. Here, we present RNA-Seq transcriptome data from OCI-AML-20, a new AML cell line with inv(3) and deletion of chromosome 7. Overall design: RNA-Seq transcriptome analysis of OCI-AML-20 cell line with three biological replicates.
Characterization of inv(3) cell line OCI-AML-20 with stroma-dependent CD34 expression.
Disease, Cell line, Subject
View SamplesERRa and ERRg are essential transcriptional regulators of cardiac metabolism and functions. Here we extend our previous studies by analyzing the transcriptome changes in ERRa/ERRg KO hearts Overall design: RNA from 16-day-old mouse hearts were used. 2-3 mice per sample, 2 samples per genotype, 4 genotypes (aHetgWT, aHetgKO, aKOgWT, aKOgKO)
Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenomic enhancer profiling defines a signature of colon cancer.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MYC regulation of a "poor-prognosis" metastatic cancer cell state.
Specimen part, Cell line
View SamplesCancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, despite the fact that distal regulatory elements play a central role in controlling transcription patterns. Here we utilize the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a unique transcriptional program to promote colon carcinogenesis.
Epigenomic enhancer profiling defines a signature of colon cancer.
Specimen part
View SamplesExpression data from ERBB2 over-expression and EGF stimulation in MCF10A cells
MYC regulation of a "poor-prognosis" metastatic cancer cell state.
Specimen part, Cell line
View SamplesExpression data from DHT stimulation vs. control in LNCaP cells
MYC regulation of a "poor-prognosis" metastatic cancer cell state.
Specimen part, Cell line
View SamplesLivers from wild-type (WT) or Ppara knock-out (Ppara KO) C57Bl6 mice were used to prepare RNA which was then processed for analysis using MoGene-2_0-st Affymetrix microarrays according to standard procedures.
The logic of transcriptional regulator recruitment architecture at <i>cis</i>-regulatory modules controlling liver functions.
Sex, Specimen part
View Samples