In contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e. reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, activation of dedifferentiation response in mammalian tissues holds an immense promise for human regenerative medicine. msx2 expression has been shown to peak at the early time points of amphibian limb regeneration. Despite this temporal importance in the heterogenous regenerating limb tissues, the potential role of msx2 in dedifferentiation was previously not addressed in salamander or mammalian muscle cells. In order to test this, we ectopically overexpressed msx2 in mammalian myotubes and profiled their transcriptomes using next generation sequencing. We identified 4964 up-regulated and 4464 down-regulated transcripts in myotubes compared to myoblasts (uninduced GFP control cells; = 1.5 fold; FDR corrected p-values < 0.01). Upon ectopic msx2 expression in myotubes, 923 transcripts were downregulated, whereas 1283 transcripts were upregulated. Based on msx2's potential role in dedifferentiation, we reasoned that the transcripts, which are normally upregulated in myotubes in comparison to myoblasts, should go down upon msx2-expression. In accord with this idea, 575 myotube-enriched transcripts were downregulated after one day of ectopic msx2 expression. Similarly, 331 myoblast-enriched transcripts were upregulated upon msx2 expression. Overall design: To extensively analyze transcriptome-wide changes upon ectopic msx2 expression in mammalian myotubes, we performed next generation RNA-sequencing (RNA-seq) on uninduced and induced isolated myotubes that have msx2 and GFP or GFP alone transgenes. As a reference for the undifferentiated state, we also sequenced the transcriptomes of uninduced myoblast cultures of these two transgenic constructs. Deep sequencing was performed using Illumina HiSeq.
Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation.
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View SamplesMicroarray analysis was performed to determine the transcriptional profiles of NKT, CD1d-aGC+ Va24-, and CD4 T cells.
A naive-like population of human CD1d-restricted T cells expressing intermediate levels of promyelocytic leukemia zinc finger.
Specimen part
View SamplesThe RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked monogenic disease associating severe learning deficit andassociated to typical facial and digital abnormalities and skeletal changes. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized.
RSK2 is a modulator of craniofacial development.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Specimen part, Cell line
View SamplesTo identify genes that require PLZF for their regulation in NKT cells, we compared the developmental stages of thymic NKT cells from wildtype and PLZF-deficient mice
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Specimen part
View SamplesFLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors
FLT3-ITDs instruct a myeloid differentiation and transformation bias in lymphomyeloid multipotent progenitors.
Sex, Specimen part
View SamplesIL13R2 overexpression promotes metastasis of basal-like breast cancers
Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis.
Specimen part, Cell line, Treatment
View SamplesAffymetrix Mouse Gene 1.0 ST Array profiles were generated from acticular cartilage derived from CBA and Str/ort mice at three ages (8W, 18W, 40W), corresponding to stages prior to, at and late after natural osteoarthritis (OA) onset in OA-prone Str/ort mice.
Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis.
Age, Specimen part
View SamplesWe used microarrays to investigate gene expression changes in tumor-bearing Pax5+/- mice
Infection Exposure is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility.
Specimen part
View SamplesBackground Accurate assessment of treatment efficacy would facilitate clinical trials of new anti-tuberculosis drugs. TB patients exhibit altered peripheral immunity which reverts during successful treatment. We hypothesised that these changes could be observed in whole blood transcriptome profiles. Methods Ex vivo blood samples from 27 pulmonary TB patients were assayed at diagnosis and during conventional treatment. RNA was processed and hybridised to Affymetrix GeneChips, to determine expression of over 47,000 transcripts. Findings There were significant changes in expression of over 4,000 genes during treatment. Rapid, large scale changes were detected, with down-regulated expression of ~1,000 genes within the first week, including inflammatory markers such as the complement components C1q and C2. This was followed by slower changes in expression of different networks of genes, including a later increase in expression of B cell markers, transcription factors and signalling molecules. Interpretation The expression of many genes is drastically altered during TB disease, with components of the humoral immune response being markedly affected. The treatment-induced restoration reflects the simultaneous suppression and activation of different immune responses in TB. The rapid initial down-regulation of expression of inflammatory mediators coincides with rapid killing of actively dividing bacilli, whereas slower delayed changes occur as drugs act on dormant bacilli and as lung pathology resolves. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity.
Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response.
Specimen part, Disease, Subject, Time
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