Wildtype mice were given saline or bleomycin by oropharyngeal instillation. After 14 days, during the fibrotic phase of the response, lungs were dissected and total RNA was extracted and used for gene expression profiling. The aim was to identify those genes regulated during the development of fibrosis in this animal model of bleomycin-induced lung fibrosis.
Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury.
Sex, Specimen part, Treatment
View SamplesTranscriptome analysis of partially degraded and fragmented RNA samples from body fluids
Exon-level expression profiling: a comprehensive transcriptome analysis of oral fluids.
No sample metadata fields
View SamplesFor Staphylococcus aureus it was shown previously that aminocoumarinecoumarin antibiotics such as novobiocin lead to immediate down-regulation of recA expression and thereby inhibition of the SOS response, the mutation frequency and the recombination capacity. Aminocoumarinecoumarin function by inhibition of the ATPase activity of the gyrase subunit B. Here we analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. By use of a novobiocin resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and Northern blot hybridization revealed that the expression of a distinct set of genes is increased (e.g. recF-gyrB-gyrA, rib operon and ure operon )), or decreased (e.g. arlRS, recA, lukA, hlgC, fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the supercoiling level in S. aureus. Thus, down-regulation of arlRS might in part compensate for the relaxing effect of novobiocin. Novobiocin resulted in down-regulation of several of arlRS repressed target genes in an arl mutant. Global analysis and gene mapping of supercoiling sensitive genes did not give indications that they are clustered in the genome. Promoter fusion assays confirmed that responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. The results indicate that molecular property of the spacers of a given promoter dictatesa given promoter rather than chromosomal topology dictates the responsiveness towards changes in supercoiling rather than chromosomal topology.
Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus.
Treatment
View SamplesWhole blood transcriptomes from a longitudinal study of 5 Malawian children who first present with severe Plasmodium falciparum malaria, and return in one month with mild malaria
Mild Plasmodium falciparum malaria following an episode of severe malaria is associated with induction of the interferon pathway in Malawian children.
Age, Specimen part, Subject
View SamplesA Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.
No sample metadata fields
View SamplesThe role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator of mitochondrial fusion, essential for the naïve-to-primed interconversion of murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their mitochondria and slightly alter their glutamine utilization. In contrast, MTCH2-/- ESCs fail to elongate their mitochondria and to alter their metabolism, maintaining high levels of histone acetylation and expression of naïve pluripotency markers. Importantly, enforced mitochondria elongation by the pro-fusion protein Mitofusin (MFN) 2 or by a dominant negative form of the pro-fission protein dynamin-related protein (DRP) 1 is sufficient to drive the exit from naïve pluripotency of both MTCH2-/- and wild-type ESCs. Taken together, our data indicate that mitochondria elongation, governed by MTCH2, plays a critical role and constitutes an early driving force in the naïve-to-primed pluripotency interconversion of murine ESCs. Overall design: Examination of WT and MTCH2 KO ESC and EpiLC mouse embryonic stem cells transcriptome
MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells.
Specimen part, Subject
View SamplesRecent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. Overall design: poly RNA-Seq was measured before, during and after conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method.
Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming.
Specimen part
View SamplesPluripotency can be induced in somatic cells by ectopic expression of defined transcription factors, however the identity of epigenetic regulators driving the progression of cellular reprogramming requires further investigation. Here we uncover a non-redundant role for the JmjC-domain-containing protein histone H3 methylated Lys 27 (H3K27) demethylase Utx, as a critical regulator for the induction, but not for the maintenance, of primed and nave pluripotency in mice and in humans. Utx depletion results in aberrant H3K27me3 repressive chromatin demethylation dynamics, which subsequently hampers the reactivation of pluripotency promoting genes during reprogramming. Remarkably, Utx deficient primordial germ cells (PGCs) display a cell autonomous aberrant epigenetic reprogramming in vivo during their embryonic maturation, resulting in the lack of functional contribution to the germ-line lineage.
The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming.
Specimen part
View SamplesHomeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxd4 during cartilage development, we observed severe defects, namely physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, we performed gene expression profiling using the Affymetrix microarray platform.
Microarray Analysis of Defective Cartilage in Hoxc8- and Hoxd4-Transgenic Mice.
Specimen part
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