The plasma protein FHR1 induces release of inflammatory cytokines IL-1ß, IL-6, IL-18 or TNFa from blood-derived human monocytes. RNA sequencing was performed from RNA of BSA- or FHR1-treated monocytes from 4 different donors. In response to FHR1, 522 monocytic genes were upregulated (gene ontology enrichment analysis), including 35 inflammation related genes, e.g. TNF. Also, G protein-coupled receptors such as EMR2/ADGRE2 were upregulated in response to FHR1. Overall design: Blood-derived monocytes were treated with BSA or FHR1, after 4h RNA was isolated. RNA of 4 donors were combined and sequenced.
Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies.
Specimen part, Treatment, Subject
View SamplesThe regeneration of diseased hyaline cartilage remains a great challenge, mainly because degeneration activities after major injury or due to age-related processes overwhelm the self-renewal capacity of the tissue. We show that repair tissue from human articular cartilage of late stages of osteoarthritis harbor a unique progenitor cell population, termed chondrogenic progenitor cells exhibiting stem cell characteristics, such as multipotency, lack of immune system activation and, in particular, migratory activity. The isolated CPC exhibit a high chondrogenic potential and were able to populate diseased tissue in vivo. Moreover, down-regulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9 and consequently the matrix synthesis potential of chondrogenic progenitor cells. Our results, while offering new insight into the biology of progenitor cells from diseased cartilage tissue, might assist future strategies to treat late stages of osteoarthritis.
Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis.
No sample metadata fields
View SamplesThe choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.
The transcription factor Otx2 regulates choroid plexus development and function.
Sex
View SamplesObjective: Physical exercise and vitamin E are considered effective treatments of nonalcoholic fatty liver and other metabolic diseases. However, vitamin E has also been shown to interfere with the adaptation to exercise training, in particular for the skeletal muscle. Here, we studied the hypothesis that vitamin E also interferes with the metabolic adaptation of the liver to acute exercise.
A Vitamin E-Enriched Antioxidant Diet Interferes with the Acute Adaptation of the Liver to Physical Exercise in Mice.
Sex, Specimen part
View SamplesHeterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 plays a pivotal role in vitamin D receptor (VDR) signaling by acting as a vitamin D response element (VDRE)-binding protein (VDRE-BP). Transcriptional regulation by active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) involves occupancy of VDRE by VDRE-BP or 1,25(OH)2D3 bound-VDR. This relationship is disrupted by over-expression of VDRE-BP and can cause a form of human hereditary vitamin D-resistant rickets (HVDRR). DNA array analyses using B-cells from an HVDRR patient and matched control defined a sub-cluster of genes where 1,25(OH)2D3-regulated transcription was abrogated by over-expression of VDRE-BP. Amongst these, the DNA-damage-inducible transcript 4 (DDIT4), an inhibitor of mammalian target of rapamycin (mTOR) signaling, was also induced by 1,25(OH)2D3 in human osteoblasts.
Gene targeting by the vitamin D response element binding protein reveals a role for vitamin D in osteoblast mTOR signaling.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
microRNA cluster 106a~363 is involved in T helper 17 cell differentiation.
Sex
View SamplesCombined analysis of mRNA and miRNA transcriptoms revealed a complex network regulating major immune regulatory signaling pathways
microRNA cluster 106a~363 is involved in T helper 17 cell differentiation.
Sex
View SamplesEmbryonic mouse brain development involves a sequential differentiation of multipotent progenitor cells into neurons and glia. Using microarrays and large 2-D electrophoresis, we investigated the transcriptome and proteome of mouse brains at embryonic days 9.5, 11.5 and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuronal differentiation. As expected, we detected numerous expression changes between the time points investigated but interestingly, the rate of alteration was about 10% to 13% of all proteins and mRNAs during every two days of development. Furthermore, up- and downregulation was balanced. This was confirmed for two additional stages of development, embryonic day 16 and 18. We hypothesize that during embryonic development, the rate of protein expression alteration is rather constant due to a limitation of cellular resources such as energy, space and free water. The similar complexity found at the transcriptome and proteome level at all stages suggests, that changes in relative concentration of gene products rather than an increased number of gene products dominate throughout cellular differentiation. We found that metabolism and cell cycle related gene products were downregulated in expression when precursor cells switched from proliferation to neuronal differentiation (day 9.5 to 11.5), whereas neuron specific gene products were upregulated. A detailed analysis revealed their implication in differentiation related processes such as rearrangement of the actin cytoskeleton as well as Notch and Wnt signaling pathways.
Transcriptome and proteome analysis of early embryonic mouse brain development.
No sample metadata fields
View SamplesMuscle contraction during exercise is the major stimulus for the release of peptides and proteins (myokines) that are supposed to take part in the benefical adaptation to exercise. We hypothesize that application of an in vitro exercise stimulus as electric pulse stimulation (EPS) to human myotubes enables the investigation of the human muscle secretome in a clearly defined model. We applied EPS for 24 h to primary human myotubes and studied the whole genome-wide transcriptional response and as well as the release of candidate myokines. We observed 183 differentially regulated transcripts with fold-changes > 1.3. The transcriptional response resembles several properties of the in vivo situation in the skeletal muscle after endurance exercise, namely significant enrichment of pathways associated with interleukin and chemokine signaling, lipid metabolism, and anti-oxidant defense; notably without increased release of creatin kinase.
Cytokine response of primary human myotubes in an in vitro exercise model.
Sex, Specimen part, Subject
View SamplesThe invasion of activated fibroblasts represents a key pathomechanism in fibrotic diseases, carcinogenesis and metastasis. Here, invading fibroblasts contribute to fibrotic extracellular matrix (ECM) formation and the initiation, progression, or resistance of cancer, respectively. To construct a transcriptome-wide signature of fibroblast invasion, we used a multiplex phenotypic 3D invasion assay using murine lung fibroblasts. Microarray-based gene expression profiles of invading and non-invading fibroblasts were highly distinct: 1049 genes were differentially regulated (>1.5-fold). An unbiased pathway analysis (Ingenuity) identified a significant enrichment for the functional clusters invasion of cells, idiopathic pulmonary fibrosis (IPF) and metastasis. Particularly, matrix metalloprotease13 (MMP13), transforming growth factor (TGF)1, Caveolin1 (Cav1), Phosphatase and Tensin Homolog (Pten), and secreted frizzled-related protein1 (Sfrp1) were among the highest regulated genes. In silico analysis by Ingenuity predicted TGF1, epidermal growth factor (EGF), fibroblast growth factor2 (FGF2), and platelet-derived growth factor (PDGF)-BB to induce invasion. As such, these growth factors were tested in the 3D invasion assay and displayed a significant induction of invasion, thus validating the transcriptome profile. Accordingly, our transcriptomic invasion signature describes the invading fibroblast phenotype in unprecedented detail and provides a tool for future functional studies of cell invasion and therapeutic modulation thereof.
Validated prediction of pro-invasive growth factors using a transcriptome-wide invasion signature derived from a complex 3D invasion assay.
Sex
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