Natural Killer (NK) cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantations (h-HSCTs) with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after h-HSCT of a donor-derived unconventional subset of CD56dim/CD16neg (uCD56dim) NK cells expressing remarkable high levels of NKG2A and low levels of NKp46. Both transcription and phenotypic profiles indicated that uCD56dim NK cells are a distinct NK cell subpopulation with features of late differentiation, yet retaining proliferative capability and functional plasticity to generate conventional CD56bright/CD16pos NK cells in response to IL-15 plus IL-18. uCD56dim NK cells represent by far the largest NK cell subset detectable in the following 7 weeks after h-HSCT and they also express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, uCD56dim NK cells displayed a defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human NK cells and to develop a novel immune-therapeutic approach by targeting the inhibitory NKG2A check point, thus enhancing NK cell alloreactivity early after h-HSCT.
The early expansion of anergic NKG2A<sup>pos</sup>/CD56<sup>dim</sup>/CD16<sup>neg</sup> natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation.
Specimen part
View SamplesPlasmodium berghei ANKA infection in mice is used as a model for human cerebral malaria, the most severe complication of Plasmodium falciparum infection. The response of brain cells such as microglia has been little investigated, and may play a role in the pathogenesis or regulation of cerebral malaria. We showed previously that microglia are activated in P. berghei infections, and that Type 1 Interferon signaling is important for activation. This dataset contains the transcriptome of brain microglia of infected mice in the presence and absence of Type I interferon signaling, with the aim of identifying the genes involved in this pathway in microglia during experimental cerebral malaria. Refererence: Capuccini et al 2016, Scientific Reports, 6:39258
Transcriptomic profiling of microglia reveals signatures of cell activation and immune response, during experimental cerebral malaria.
Sex, Specimen part, Treatment
View SamplesLangerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. In contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, we found that oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103+CD11blow (CD103+LCs) and CD11b+CD103- (CD11b+LCs) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103+LCs originate from pre-DCs, whereas CD11b+LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with their epithelial position, morphology and expression of LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DCs and monocytic) in steady state Overall design: The following cells were isolated from mice (2-4 replicates): Lung DCs, mucosal CD103+ LC, mucosal CD11b+ LC, Skin LC. Transcriptome analysis was performed.
Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.
Specimen part
View SamplesTo determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients subjected to conrolled reoxygenation cardiopulmonary bypass, we collected myocardial samples at the end of the ischemic time. The transcriptional profile of the mRNA in these samples was measured with gene array technology
Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.
Specimen part
View SamplesTo determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients subjected to hyperoxic/standard cardiopulmonary bypass, we collected myocardial samples at the end of the ischemic time. The transcriptional profile of the mRNA in these samples was measured with gene array technology
Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.
Specimen part
View SamplesIdentifying the genes underlying quantitative trait loci (QTL) for disease has proven difficult, mainly due to the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals and test candidate genes. In addition to identifying the causative genes, defining the pathways that are affected by these QTL is of major importance as it can give us insight into the disease process and provide evidence to support candidate genes. In this study we mapped three significant and one suggestive QTL on Chromosomes (Chrs) 1, 4, 15, and 17, respectively, for increased albumin excretion (measured as albumin-to-creatinine ratio) in a cross between the MRL/MpJ and SM/J mouse inbred strains. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL. Among these were the glycan degradation, leukocyte migration, and antigen presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL, but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease.
Uncovering genes and regulatory pathways related to urinary albumin excretion.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Off-pump coronary artery bypass surgery is associated with fewer gene expression changes in the human myocardium in comparison with on-pump surgery.
No sample metadata fields
View SamplesWe treated logarithmically growing cultures of E.coli with a sub-lethal dose of an antimicrobial arylamide compound (PMX 10070) and Polymyxin B sulfate to measure transcriptional responses in an effort to understand mechanism of action
Antibacterial mechanism of action of arylamide foldamers.
No sample metadata fields
View SamplesTo investigate changes in cardiac transcription profiles caused by off-pump cardiac surgery, we collected myocardial samples, prior and after grafting, from patients undergoing off-pump coronary revascularization surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Changes in transcriptional profiles can be correlated with the stress response of heart to off-pump surgery.
Off-pump coronary artery bypass surgery is associated with fewer gene expression changes in the human myocardium in comparison with on-pump surgery.
No sample metadata fields
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