Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1?mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms. Overall design: RNA-Seq time couse of muscle volumetric muscle loss injury healing with controls
Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury.
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View SamplesWe have previously reported that tyrosol (TYR), one of the main phenols in extra virgin olive oil (EVOO), promotes lifespan extension in the nematode Caenorhabditis elegans, also inducing a stronger resistance to thermal and oxidative stress in this animal model. Although the influence of several longevity-related genes in these effects has been reported by our group, we decided to perform a whole genome DNA-microarray approach in order to identify other genes and molecular pathways further involved in TYR effects on C. elegans longevity. Microarray analysis identified 208 differentially expressed genes (206 overexpressed and 2 underexpressed) when comparing TYR-treated nematodes with non-treated controls. Many of these genes seem linked to processes such as regulation of growth, transcription, reproduction, lipid metabolism and body morphogenesis. Data obtained by microarray was validated by qRT-PCR analysis of selected genes. Our results confirm that several important cellular mechanisms related to longevity are influenced by TYR treatment in this animal model. Moreover, we detected an interesting overlap between the expression pattern elicited by TYR and those induced by other dietary polyphenols known to extend lifespan in C. elegans, such as quercetin and tannic acid.
Gene expression profiling to investigate tyrosol-induced lifespan extension in Caenorhabditis elegans.
Treatment
View SamplesWe describe 9 CLL patients who underwent a spontaneous clinical regression. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of VH3-30 gene in 2. The light chain variable region genes were mutated in 6/8 cases, with the usage of V4-1 gene in 3. Microarray analysis of CLL cells revealed a distinctive genomic profile. The number of activated T lymphocytes expressing IFN-, TNF- and IL-4 was similar between CLL in spontaneous regression and healthy individuals.
Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Increased chronic lymphocytic leukemia proliferation upon IgM stimulation is sustained by the upregulation of miR-132 and miR-212.
Sex, Age, Specimen part, Disease
View SamplesIn order to investigate a potential involvement of miRNAs in BCR stimulation, in the present work we first evaluated their expression following IgM cross-linking in CLL cells, as well as in healthy B lymphocytes. Next, to infer putative miRNA targeting networks, we combined miRNA profiling results with gene expression and functional analyses
Increased chronic lymphocytic leukemia proliferation upon IgM stimulation is sustained by the upregulation of miR-132 and miR-212.
Sex, Age, Specimen part, Disease
View SamplesProtein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Specimen part, Cell line
View SamplesWe used microarray analysis to investigate if keratinocytes excert an immuno-inflammatory response towards streptococcal M1 protein.
Vigilant keratinocytes trigger pathogen-associated molecular pattern signaling in response to streptococcal M1 protein.
Specimen part, Cell line
View SamplesAnoxia induces several heat shock proteins and a heat pre-treatment can acclimatize Arabidopsis seedlings to a subsequent anoxic treatment. In this work we analyzed the response of Arabidopsis seedlings to anoxia, heat and a combined heat+anoxia stress. A significant overlapping between the anoxic and heat shock responses has been observed by whole-genome microarray analysis.
The heat-inducible transcription factor HsfA2 enhances anoxia tolerance in Arabidopsis.
Age, Treatment
View SamplesArabidopsis thaliana ecotype Columbia glabra were grown for 4 days in the dark without added sucrose. Samples were subsequently kept for 6h either [1] under aerobic conditions, [2] under anoxia in absence of sucrose or [3] under anoxia in presence of sucrose.
A genome-wide analysis of the effects of sucrose on gene expression in Arabidopsis seedlings under anoxia.
No sample metadata fields
View SamplesInduced pluripotent stem cells (iPSCs) offer opportunity for insight into the genetic requirements of the X chromosome for somatic and germline development. Turner syndrome is caused by complete or partial loss of the second sex chromosome; while more than 90% of Turner cases result in spontaneous fetal loss, survivors display an array of somatic and germline clinical characteristics. Here, we derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We analyzed gene expression profiles of derived iPSCs and in vitro differentiated cells by single cell qRT-PCR and RNA-seq. We whoed that two X chromosomes are not necessary for reprogramming or pluripotency maintenance. Genes that escape X chromosome inactivation (XCI) between control iPSCs and those with X chromosome aneuploidies revealed minimal expression differences relative to a female hESC line. Moreover, when we induced germ cell differentiation via murine xenotransplantation of iPSC lines into the seminiferous tubules of busulfan-treated mice, we observed that undifferentiated iPSCs, independent of X chromosome composition, when placed within the correct somatic environment, are capable of forming early germ cells in vivo. Results indicate that two intact X chromosomes are not required for germ cell formation; however, clinical data suggest that two sex chromosomes are required for maintenance of human germ cells. Overall design: RNA-seq of H9 cells, iPSCs from Turner syndrome and control individuals and in vitro differentiated cells
Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies.
No sample metadata fields
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