Background
Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2-cell responses.
Specimen part, Treatment
View SamplesAcute kidney injury (AKI) is associated with an abrupt loss of kidney function that results in significant morbidity and mortality. Considerable effort has focused around the identification of diagnostic biomarkers and the analysis of molecular events. Most studies have adopted organ-wide approaches that do not fully capture the interplay among different cell types in the pathophysiology of AKI. To extend our understanding of molecular and cellular events in AKI, we developed a mouse line that enables the identification of translational profiles in specific cell types by CRE recombinase-dependent activation of an eGFP-tagged L10a ribosomal protein subunit, and consequently, translating ribosome affinity purification (TRAP) of mRNA populations. By utilizing cell-type specific CRE-driver lines, in this study we identify distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Cell-specific translational expression profiles were uncovered 24 hours after IRI from four populations enriched for distinct anatomical and cellular subgroups: nephron, interstitial cell populations, vascular endothelium, and macrophages/monocytes by Affymetrix microarray.
Cell-specific translational profiling in acute kidney injury.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.
Sex, Age, Specimen part
View SamplesMyasthenia gravis (MG) is a relatively rare autoimmune neuromuscular disorder. Monozygotic twin studies indicate that discordance rate in MG is about 70-60%, suggesting that despite identical DNA unknown factors contribute to disease development. The aim of the current study was to identify novel disease-associated genes in purified monocytes, including both genes associated with predisposition or with disease course, using the unique model of MZ twins. Thus the transcriptome and methylome were compared between twins discordant and concordant for the diseases, as well as MG singletons, and healthy controls. Several transcripts associated with immune homeostasis and inflammation resolution were highlighted in the current study. High similarity between the healthy and the MG discordant twins found, suggest that genetic predisposition may have a stronger contribution then previously assumed. In addition, results suggest that numerous small changes in expression and DNA methylation might contribute to disease onset making it more difficult to pick up
Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.
Sex, Age, Specimen part
View SamplesAlthough nuclear transfer allows the reprogramming of somatic cells to totipotency, little is known concerning the kinetics by which it takes place or the minimum requirements for its success. Here, we demonstrate that reprogramming can be achieved within a few hours and a single cell-cycle as long as two key constraints on reprogramming are satisfied. First, the recipient cell chromosomes must be removed during mitosis. Second, the nuclear envelope of the donor cell must be broken down and its chromosomes condensed, allowing an embryonic nucleus to be constructed around the incoming chromosomes. If these requirements are not met, then reprogramming fails and embryonic development arrests. These results point to a central role for processes intimately linked to cell division in mediating efficient transitions between transcriptional programs.
Reprogramming within hours following nuclear transfer into mouse but not human zygotes.
Specimen part
View SamplesHuman CD4+ T cells and CD14+ monocytes from healthy donors were co-cultured with anti-CD3 for three days in the presence or absence of TNF-alpha mAb (Adalimumab). Classical Th17 cells (Th17) or those generated in the presence of the inhibitor (iTh17) were then sorted and analyzed by full transcriptome microarray analysis.
TNF-α blockade induces IL-10 expression in human CD4+ T cells.
Specimen part, Treatment, Subject
View SamplesType 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance.
Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels.
Cell line
View SamplesSelf-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engrafted in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them.
Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Specimen part
View SamplesDetermination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis.
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Specimen part
View Samples