Endocardial (EE) and Aortic (AE) endothelial cells were isolated from the same two rats, pooled (EE and AE kept separately) and cultured for 2 passages. Culture conditions and confluence of EE and AE cell cultures were kept as identical as possible. RNA was isolated and the expression profile of both endothelial cell types was compared using the Affymetrix rat genome U34A array.
Molecular diversity of cardiac endothelial cells in vitro and in vivo.
No sample metadata fields
View SamplesEpidemiologic and animal studies implicate overconsumption of fructose in the development of non-alcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remains largely unknown. We present evidence supporting the essential function of the lipogenic transcription factor ChREBP in mediating adaptation response to fructose and protecting against fructose-induced hepatotoxicity. High-fructose diet (HFrD) activates hepatic lipogenesis via a ChREBP-dependent manner in wildtype mice, while inducing steatohepatitis in Chrebp-KO mice. In Chrebp-KO mouse livers, HFrD reduces levels of molecular chaperones and activates the CHOP-dependent unfolded protein response, whereas administration of chemical chaperone or Chop shRNA rescues liver injury. Gene expression profiling revealed elevated expression of cholesterol biosynthesis genes in Chrebp-KO livers after HFrD, in parallel with increased abundance of nuclear SREBP2.
Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity.
Specimen part
View SamplesTAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (?NLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display a loss of endogenous mouse nuclear TDP-43 as well as dramatic changes in gene expression as measured by microarray. Here, we analyze RNA-sequencing data from the ?NLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice and High Throughput Sequencing of RNA isolated by CrossLinking ImmunoPrecipitation (HITS-CLIP) data of TDP-43’s RNA binding targets to further investigate the dysregulation of gene expression in the ?NLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ?NLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains. Overall design: RNAseq of bigenic (n=4) ?NLS-hTDP-43 and control nontransgenic (n=4) mouse cortex
Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin.
No sample metadata fields
View SamplesWe aimed at finding differently expressed genes in whole blood cells of African children with asymptomatic Plasmodium falciparum infection (A), uncomplicated malaria (U), severe malarial anemia (A) and cerebral malaria (Ce) compared one to another and to healthy children (Co).
The blood transcriptome of childhood malaria.
Specimen part
View SamplesWe aimed to identify genes that are regulated at downstream of FGFR1/KLB receptor complex in brown adiposetissues of adult male mice on high fat diet by injecting anti-FGFR1/KLB agonisticantibody or human FGF21.
Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex.
Specimen part
View SamplesThe comparative advantages of RNA-Seq and microarrays in transcriptome profiling were evaluated in the context of a comprehensive study design. Gene expression data from Illumina RNA-Seq and Affymetrix microarrays were obtained from livers of rats exposed to 27 agents that comprised of seven modes of action (MOAs); they were split into training and test sets and verified with real time PCR.
The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.
Sex, Specimen part
View SamplesTo identify candidate genes involved in enhanced tumorigenicity and metastasis of CD90+ esophageal tumor-initiating cells.
A CD90(+) tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer.
Specimen part, Cell line
View SamplesSamples of adherent and suspension cells undergoing reprogramming were collected at day 0, day2, day6, day15 (with doxycycline) and day25 (without doxycycline).
Derivation, expansion and differentiation of induced pluripotent stem cells in continuous suspension cultures.
Specimen part
View SamplesSMARCA2 and SMARCA4 are two mutually exclusive ATPase subunits of SWI/SNF complex. SMARCA4 deficient lung cancer population selectively depend on SMARCA2 for cancer growth phenotype. Rescue experiments with ectopic expression of wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4 highlight that ATPase domain is the drug target.
The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies.
Specimen part, Cell line
View SamplesUsing a CML mouse model, we identified differences in gene expression between leukemic compared with non-leukemic LTHSC, including increased expression of the thrombopoietin (THPO) receptor MPL. LTHSC expressing high levels of MPL showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro, and increased leukemogenic capacity in vivo compared to LTHSC with low MPL expression. Although both G0 and S-phase subpopulations were increased in MPL expressing LTHSC, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSC resulted in reduced THPO-induced JAK/STAT signaling and leukemogenic potential. Similar observations were made with LTHSC from CML patients. MPL expressing LTHSC demonstrated reduced sensitivity to BCR-ABL TKI treatment but demonstrated increased sensitivity to JAK inhibitors. Our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSC, and suggest that MPL-expressing CML stem cells are critical targets for therapy. Overall design: To evaluate heterogeneity in LSC potential, donor LTHSC from SCL-tTA/BCR-ABL mice (200 cells/mouse) were transplanted into a cohort of congenic FVBN mice. Recipient mice were followed for engraftment of donor CML cells and development of CML. LTHSCs were isolated from leukemic and non-leukemic recipient mice and global gene expression was analyzed using RNA-Seq.
Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.
Specimen part, Subject
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