We investigated an acute kidney injury (AKI) model in rats induced by cisplatin (Cp) administration. The cisplatin is widely used since its biochemical and histopathological characteristics are representative of drug-induced AKI in humans. Male Wistar rats were dosed once ip with 0, 1 and 3 mg/kg cisplatin. Tubular necorsis was observed histopathologically in all treated rats and war recovery on day 26. Gene expression profiling of the kidney cortex with microarrays 3, 5, 8, and 26 days after single administration of 3mg/kg Cp revealed a major profile pattern characterized by maximally increased and decreased mRNA levels on day 8, with clear changes already found 3 days after treatment for about half of the mRNAs. The mRNA expression pattern after administration of 1mg/kg Cp was overall similar, yet with a dose-dependent smaller fold-change. In summary we found 274 mRNAs showing significantly altered levels in the kidney of which 162 were increased and 112 decreased, respectively. Functional interpretation of the proteins encoded by these mRNAs revealed induction of a DNA damage response likely caused by the known molecular activity of Cp as DNA alkylating agent. Increased mRNAs associated with apoptosis (encoded by the corresponding genes like B-cell lymphoma 3-encoded protein, Bcl3; mouse double minute 2 homolog, Mdm2; p21/WAF1 also known as cyclin-dependent kinase inhibitor 1), cell cycle regulation (encoded by the corresponding genes like Cyclin-G1, Ccng1; B-cell translocation gene 2, Btg2) and stress response may have partly been induced by the DNA damage, but also by the kidney damage associated with Cp administration. Increased levels of mRNAs indicating regeneration (encoded by the corresponding genes like SPARC- related modular calcium-binding protein 2, Smoc2; Tenascin C, Tnc) and decreased levels of mRNAs coding for proteins related to kidney function, indicating dedifferentiation, are likely related to the observed kidney injury.
Comparison of the MesoScale Discovery and Luminex multiplex platforms for measurement of urinary biomarkers in a cisplatin rat kidney injury model.
Sex, Specimen part
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Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesWe analyzed the transcriptional signatures of mouse bone marrow-derived macrophages (BMDM) at different times after infection with promastigotes of the protozoan parasite Leishmania major.
Transcriptomic signature of Leishmania infected mice macrophages: a metabolic point of view.
Specimen part
View SamplesLeukemia cells are considered developmentally 'frozen', and their phenotype is thought to reflect their stage of origin. To gain insights into the cell population from which T-ALL arises, we compared by global gene expression profiling T-ALL samples (n = 10) to different stages of T cell development, following the order from early thymic progenitor (ETP), to triple negative (TN) TN2, to TN3, to TN4, to immature single positive (ISP), to double positive (DP) thymocytes.
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesWild type thymi were transplanted into a competitive (wild type hosts), or non-competitive (Rag2-/-c-/-KitW/Wv hosts) environment. Triple negative 2 and 3 (TN2/3) stages were sorted 14 days afetr transplantation and separated for cells of host or donor origin.
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesTranscriptome was assessed in the transitions from the normal thymus (with regular progenitor turnover), to a thymus devoid of extrinsic progenitor competition for 10 weeks, to fully malignant T cell acute lymphoblastic leukemia (T-ALL).
Cell competition is a tumour suppressor mechanism in the thymus.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Sex, Age, Specimen part, Treatment
View SamplesHdac1 and 2 are important regulators of developmental processes. In this study we created microglia specific compound Hdac1 and Hdac2 knock out mice. Pre-natal ablation of both Hdac1 and 2 from microglia leads to reduced cell number and altered cell morphology. To investigate how Hdac1 and 2 knock out in microglia alters cellular gene expression profile we carried out RNA-seq analysis at different time points. Overall design: We used FACS sorted microglia cells from control and Hdac1/2fl/flCx3cr1Cre (constituitive knockout) or Hdac1/2fl/flCx3cr1CreERT2 (inducible) mice at different time points viz. Embryonic day 16 (E16 - inducible knockout only), Post natal day 0 (P0), 2 and 6 weeks after birth
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Age, Treatment, Subject
View SamplesEpigenetic alterations has been implicated in the pathology of several neurodegenerative diseases. To investigate the role of microglial Hdac1 and 2 in the pathogenesis of Alzheimer's disease (AD), we created microglia specific compound Hdac1 and Hdac2 knock out mice in 5X FAD background. Genetic ablation of Hdac1 and 2 from microglia reduced amyloid plaque burden and improved spatial learning and memory function.
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Sex, Specimen part
View SamplesTo assess natural variation of downstream auxin responses we subjected 7 different arabidopsis ecotypes to a time course of auxin treatments. 7d-old seedlings grown in liquid culture have been treated for 0, 30 min, 1h and 3h with 1 M IAA.
Natural variation of transcriptional auxin response networks in Arabidopsis thaliana.
Specimen part
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