Myostatin (Mstn) knockout mice exhibit large increases in skeletal muscle mass. However, relatively few of the genes that mediate or modify MSTN effects are known. In this study, we performed co-expression network analysis using whole transcriptome microarray data from Mstn-null and wild-type mice to identify genes involved in important biological processes and pathways related to skeletal muscle and adipose development.Genes differentially expressed between wild-type and Mstn-null mice were identified at 13.5 d.p.c. and 35 days after birth (d35) and further analyzed for shared DNA motifs using DREME.
Gene co-expression network analysis provides novel insights into myostatin regulation at three different mouse developmental timepoints.
Age, Specimen part
View SamplesDuring organogenesis of the intestine, reciprocal crosstalk between the endodermally-derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation. Though both of these tissue layers participate in patterning, the mesenchyme is thought to play a prominant role in the determination of epithelial phenotype during development and in adult life. However, the molecular basis of this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in separated mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional crosstalk. We also catalog the most highly enriched transcription factors in both compartments and find evidence for a major role for Hnf4alpha and Hnf4 gamma in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue-restricted in their expression, mesenchymally-enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely non-tissue specific.
Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk.
No sample metadata fields
View SamplesWe analysed the capacity of THP-1 cells (differentiated to macrophagoid cells) to recognize RNA sequences via pattern recognition receptors in vitro. Gene expression was analysed by RNA-Microarray. Cytokine production was analysed by ELISA assays.
Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA.
Cell line, Treatment
View SamplesElectrochemical gradients of monovalent cations across the plasma membrane (high intracellular potassium, [K+]i vs low intracellular sodium, [Na+]i) are created by the Na+,K+-pump and determine a large variety of physiologically important processes. We hypothesized that transcriptomics changes triggered by hypoxia are at least partially caused by Na+i/K+i-mediated excitation-transcription coupling .
Transcriptomic changes triggered by hypoxia: evidence for HIF-1α-independent, [Na+]i/[K+]i-mediated, excitation-transcription coupling.
Specimen part
View SamplesHost-environment interfaces such as the dermis comprise tissue macrophages as the most abundant resident immune cell type. Diverse tasks, i.e. to resist against invading pathogens, to attract bypassing immune cells from penetrating vessels and to aid tissue development and repair require a dynamic postnatal coordination of tissue macrophages specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into distinct subsets by adapting single cell transcriptomics, fate-mapping and tissue imaging. We thereby identified a small phenotypically and transcriptionally distinct subset of embryo-derived skin macrophages that was maintained and largely excluded from the overall postnatal exchange by monocytes. These macrophages specifically interacted with dermal sensory nerves, surveilled and trimmed the myelin sheets and regulated axon sprouting after mechanical injury. In summary, our data show long-lasting functional specification of macrophages in the dermis that is driven by step-wise adaptation to guiding structures and ensures codevelopment of ontogenetically distinct cells within the same compartment. Overall design: Single Cell Sequencing was performed on CD45+CD11b+CD64+Lin-(lineage B220, CD3, NK1.1, Siglec-F, Ly6G) CX3CR1 (low, mid, high) macrophage subsets from mouse dermis after enzymatic digestion
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves.
Age, Specimen part, Cell line, Subject
View SamplesBackground: Diverticular disease is a significant healthcare burden in the United States. Younger diverticulitis patients are at increased risk for recurrence. How the molecular pathophysiology differs from those that develop disease at an older age is not understood. We aimed to profile the colonic transcriptome from younger versus older diverticulitis patients to identify differential biological pathways contributing to disease. Methods: We performed RNA-seq on full-thickness sigmoid colon tissue obtained at the time of surgery on diverticulitis patients (n=26) diagnosed at a younger age (<42 years old) or at an older age (>65 years old). Viral reads were identified from the RNA-seq dataset and associated with clinical metadata and the host transcriptome. HHV-6 positivity was evaluated in diverticulitis patients by PCR and immunofluorescence. Patient sera was profiled for HHV-6 using qPCR and ELISA to detect anti-HHV-6 antibodies. Results: Using RNA-seq, diverticulitis patients were profiled for differential expression associated with age of diagnosis. A subset of younger diverticulitis patients (diverticulitis colonic transcriptome-viral signature (DCT-VS)) demonstrated increased expression of anti-viral response genes. We identified viral transcripts in the RNA-seq dataset and found HHV-6 transcripts negatively correlated with DCT-VS. Younger patients more frequently displayed evidence of HHV-6 infection through DNA analysis and immunofluorescence of colonic tissue. During acute disease, HHV-6 DNA was detected in the serum but was absent during disease quiescence. Conclusions: Patients diagnosed with diverticulitis at a younger age demonstrate reactivation of HHV-6 in the sigmoid colon that remains persistent. Future studies to assess the role of pathogenicity and the use of anti-virals for acute uncomplicated diverticulitis should be considered. Overall design: Examination of full-thickness sigmoid colon tissue from 26 diverticulitis patients, including 13 diagnosed at an younger age (<42 years old) and 13 diagnosed at an older age (>65 years old)
A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.
Sex, Specimen part, Race, Subject
View SamplesThe MYB gene family encodes transcription factors with a diverse range of functions in Arabidopsis. This study demonstrated that MYB5, which is expressed in trichomes and seeds, plays a central role in trichome and seed development. A microarray analysis of myb5 seeds identified other members of the MYB5 regulatory network.
The Arabidopsis MYB5 transcription factor regulates mucilage synthesis, seed coat development, and trichome morphogenesis.
No sample metadata fields
View SamplesStrigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected. Furthermore, we tested the response of patient-matched conditionally reprogrammed normal and prostate cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis compared to their normal counterpart cells. Treatment of cancer cells with strigolactone analogues was hallmarked by increased expression and activity of genes involved in stress signaling, cell cycle arrest and apoptosis. All five strigolactone analogues induced G2/M cell cycle arrest, accompanied with a decrease in the expression level of cyclin B1. Apoptosis was marked by increased percentages of cells in the sub-G1 fraction and was confirmed by Annexin V staining. In conditionally reprogramed matched tumor and normal prostate cells, the cleavage of PARP1 confirmed the specific increase in apoptosis of tumor cells. In summary, Strigolactone analogues are promising candidates for anticancer therapy by their ability to specifically induce cell cycle arrest, cellular stress and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.
Strigolactone analogues induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells.
Cell line, Time
View SamplesHuman mesenchymal stem cells (hMSCs) were transduced using lentivirus containing the the triple fusion reporter gene fluc-mrfp-ttk. Microarray studies of hMSCs after transduction with the triple reporter genes using lentivirus were performed to study the effects of transduction on stem cell properties using an oligonucleotide human microarray. Transduced cells were sorted by FACS. Cells with high and low signals were ftacrtionated, and gene expression profiles were determined.
Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging.
No sample metadata fields
View SamplesThis study shows that the TLR4/MyD88 pathway in intestinal mesenchymal cells promotes intestinal carcinogenesis in the APCmin mouse model. Overall design: 3' RNA-Seq (QuantSeq) profiling of ColVIcre+ wt and MyD88 knockout primary mouse intestinal mesenchymal cells before and after treatment with LPS for 6 hours. 3 replicates per group.
Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis.
Specimen part, Cell line, Treatment, Subject
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