We study the global gene expression profiles of BKV viremia and nephropathy patients using microarrays in order to better understand the immunologic response to polyomavirus BK (BKV).
Genomics of BK viremia in kidney transplant recipients.
Specimen part, Disease
View SamplesWe investigated the clinical, histopathologic and genomic features of donor-specific antibody (DSA) +/C4d- and DSA-/C4d- transplant glomerulopathy (TGP) using microarrays. Comparison of the gene expression profiles of DSA-/C4d- TGP biopsies with ptc+g score > 1 to normal and IFTA (Interstitial Fibrosis and Tubular Atrophy) biopsies by microarrays revealed increased expression of quantitative cytotoxic T cell--associated transcripts (QCAT). However, CAMR (chronic antibody-mediated rejection) and DSA+/C4d- TGP had increased expression of QCAT, interferon-gamma and rejection induced, constitutive macrophage-associated, natural killer cell-associated, and DSA selective transcripts. B cell and endothelial cell associated transcripts expression were upregulated only in CAMR biopsies. Our results suggest that while DSA+/C4d- TGP should be classified under CAMR, DSA-/C4d- TGP with ptc+g score > 1 probably develops through a chronic cellular immune response.
The clinical and genomic significance of donor-specific antibody-positive/C4d-negative and donor-specific antibody-negative/C4d-negative transplant glomerulopathy.
Specimen part
View SamplesWe study the global gene expression profiles of TGP patients with or without graft loss to determine if a clinical and/or gene expression profile can predict allograft survival.
Clinical, Histological, and Molecular Markers Associated With Allograft Loss in Transplant Glomerulopathy Patients.
Specimen part
View SamplesThe presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection.
A pathogenesis-based transcript signature in donor-specific antibody-positive kidney transplant patients with normal biopsies.
Specimen part
View SamplesSecreted MOdular Calcium-binding protein-2 (SMOC2) belongs to the SPARC (Secreted Protein Acidic and Rich in Cysteines) family of matricellular proteins whose members are known for their secretion into the extracellular space to modulate cell-cell and cel Overall design: mRNA sequencing of mouse kidney of wildtype and Smoc2 transgenic mice with and without 7 day unilateral uretal obstruction intervention
Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation.
Treatment, Subject
View Sampleswt1a:GFP labels a population of subepicardial cells in the uninjured ventricle. Here we compare the expression profile of wt1a:GFP-positive cells to the rest of the cells of the ventricle. Overall design: Four paired biological replicates of wt1a:GFP-positive and wt1a:GFP-negative cells obtained from pools of 3-5 zebrafish heart ventricles.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
No sample metadata fields
View SamplesContrary to mammals, zebrafish regenerate their heart upon cryoinjury of the cardiac ventricular apex. Regeneration is preceed by a fibrotic response. To understand the contribution of different cell sources to zebrafish cardiac fibrosis we performed an RNASeq including endocardial kdrl:mCherry cells from an uninjured heart, and activated endocardial kdrl:mCherry cells, postnb:citrine fibroblasts and the rest of the cells at 7 days post injury. Overall design: Three to six biological replicates consisting of different cell types obtained from the ventricular apex.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
No sample metadata fields
View SamplesContrary to mammals, zebrafish regenerate their heart upon cryoinjury of the ventricular apex. Regeneration is preceeded by a transient fibrotic response. Here we compare the expression profile of fibroblast-like cells at 7 different time points of fibrosis resolution. Using a postnb:CreERT2; ubb:loxP-GFP-loxP-mCherrycz1701 double transgenic line, we permanently label cells that expressed postnb at 3 and 4 days post injury (dpi) with mCherry by administration of 4-OHT. We sequenced mCherry-labelled cells obtained from the ventricular apex at 7 and 60 dpi. Overall design: postnb-derived cells were FAC sorted from a pool of three to five biological samples. Four pools were collected at 7 dpi and three at 60 dpi. RNA was extracted from those pools and further processed for transcriptome analysis.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
No sample metadata fields
View SamplesGlobal energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis.
Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition.
Specimen part, Time
View SamplesThe Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions. Overall design: Transcriptomic analysis comparing single Rbpj mutant and control mouse morulae. RNA was isolated from individual E2.5 embryos from two litters. 3 mutant and 3 control embryos were used for analysis.
Transitions in cell potency during early mouse development are driven by Notch.
Specimen part, Subject
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