Transcriptome profiling of primary monocytes from XLA patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE89980 | GEO | 2017/08/31
SECONDARY ACCESSION(S): PRJNA354347
REPOSITORIES: GEO
Similar Datasets
Project description:Saturated very long-chain fatty acids (VLCFA, ≥ C22), enriched in brain myelin and innate immune cells, accumulate in X-linked adrenoleukodystrophy (X-ALD). The severest form, inherited dysfunction of the VLCFA transporter ABCD1, underlying X-ALD, causes brain myelin destruction with infiltration of pro-inflammatory skewed monocytes/macrophages. How VLCFA levels relate to macrophage activation is unclear. Using whole transcriptome sequencing of X-ALD macrophages, we revealed that VLCFAs prime human macrophage membranes for inflammation and increase factors involved in chemotaxis and invasion. When applied externally, mimicking lipid destruction in X-ALD lesions, VLCFAs did not activate toll-like receptors in healthy cells but provoked pro-inflammatory responses through scavenger receptor CD36-mediated uptake, cumulating in JNK signalling and expression of matrix degrading enzymes and chemokine release. Following pro-inflammatory LPS-activation, VLCFA accumulated in healthy macrophages but were rapidly cleared with onset of resolution by increasing VLCFA degradation through liver-X-receptor mediated upregulation of ABCD1. ABCD1 deficiency impaired VLCFA homeostasis and prolonged pro-inflammatory gene expression. Our study uncovers a pivotal role for ABCD1, a protein linked to neuroinflammation, and associated peroxisomal VLCFA degradation in regulating macrophage plasticity.
2022-11-09 | GSE217140 | GEO
Project description:* To determine the depth of coagulation which is possible in human liver tissue using the saline linked RF Surface ablation with the Tissue Link floating ball.
* To determine the efficacy of the technique on surface liver tumors using saline linked RF surface ablati
* To determine a safe (non-popping upper limit) of power per area that will permit a 1 cm depth of tissue destruction without inflow occlusion an da 2 cm depth with inflow occlusion.
| 2069923 | ecrin-mdr-crc
Project description:MicroRNA expression levels in the lymphoblastic cells of prostate cancer patients and their healthy brothers from HPCX1 linked prostate cancer families were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to prostate cancer.
2011-12-31 | GSE24201 | GEO
Project description:Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph-) myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62-CCR2- (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ.
| S-EPMC4900622 | biostudies-literature
Project description:TSLPR+ and TSLPR- monocytes were isolated form 3 adult healthy donors and stimulated with LPS. RNA-sequencing has been performed using Illumina technology.
2017-03-28 | E-MTAB-4996 | biostudies-arrayexpress
Project description:Protein glycosylation is ubiquitous and plays critical roles in biology. However, study of O-linked glycoproteome (O-glycoproteome), a major type of protein glycosylation, has been severely impeded due to paucity of technology. We presented a chemoenzymatic strategy for extraction of site-specific O-linked glycopeptides (SOGO), which enabled simultaneous enrichment and identification of O-linked glycosylation sites (O-glycosites) in an unprecedented depth. Central to SOGO is a tandem-use of solid-phase capture of peptides and an O-linked glycan (O-glycan) dependent endoprotease named OpeRATOR. Interestingly, OpeRATOR requires O-glycan to specifically cleave the N-terminus of glycan-occupied Ser and Thr leading to unambiguous identification of O-glycosites and corresponding glycoproteins. The identified O-glycosites facilitated downstream determination of microheterogeneity of intact O-linked glycopeptides (O-glycopeptides). We benchmarked the method using human serum and identified 805 peptides containing 777 O-glycosites from 1,345 site-specific O-glycopeptides and 302 glycoproteins. We applied the method to study change of protein-specific O-glycosylation in human T cells infected with human immunodeficiency virus (HIV-1). Strikingly, 1404 peptides containing 1,352 O-glycosites from 577 glycoproteins were identified. In addition, altered site-specific O-linked glycosylation (O-glycosylation) during HIV infection of T cells were observed. In total, 1989 O-glycosites from 789 glycoproteins were precisely pinpointed from human serum and T cells. We observed conserved motifs for O-glycoproteome. Finally, ontology analysis revealed diverse roles for O-glycoproteins arguing broad application of our method to study biology in respective to protein O-glycosylation.
2022-02-28 | PXD007895 | Pride
Project description:Maps of open chromatin in three primary human blood cell types of the myeloid lineage (megakaryocytes, erythroblasts and monocytes) using the formaldehyde-assisted isolation of regulatory elements method followed by next-generation sequencing (FAIRE-seq). We also generated FAIRE-seq data in the megakaryocytic cell line CHRF-288-11. In addition to our data sets, we retrieved FAIRE-seq data for the erythroblastoid cell line K562 (ENCODE Project Consortium 2012) and pancreatic islets (Gaulton et al. 2010), and reanalyzed these data sets using the same methodology.
2013-04-08 | GSE37916 | GEO
Project description:TGFBI associated Corneal Dystrophies (CD) are a group of inherited protein folding disorders linked to the mutation in the TGFBI gene. The resultant mutant protein (TGFBIp) is deposited as insoluble protein aggregates in various layers of the cornea leading to corneal opacity and poor vision. Depending on the type of mutation the deposits may be classified as amyloid fibrillar type, amorphous globular aggregates or a mixed form of both fibrils and amorphous aggregates. However, the molecular mechanism of the mutant-induced amyloidosis is not fully understood. This study aimsto characterize truncated peptides enriched in the amyloid aggregates and to identify the protein composition of the corneal aggregates derived from dystrophic patients using LC-MS/MS and compare the data with normal control cornea. We have identified several amyloid associated proteins, non-fibrillar amyloid associated proteins and TGFBIp as the major component of the corneal deposits. The results suggest that Apolipoprotein A-IV, Apolipoprotein E and Serine protease HtrA1 to be significantly enriched in the corneal deposits compared to the normal cornea. Comparative analysis of peptides from corneal deposits of patient and control identified several peptides of TGFBIp which are enriched in patient tissue and may form the core of corneal amyloids. Most of the peptides represent the 4th FAS-1 domain of the protein. Biophysical studies of two such peptides (G515DNRFSMLVAAIQSAGLTETLNR533 and Y571HIGDEILVSGGIGALVR588) demonstrate that they readily form amyloid fibrils under physiological conditions, confirming their intrinsic propensity to form amyloid fibrils. The identification of proteins which are involved in other protein misfolding disorders as well as identification of peptides from TGFBIp which form -amyloid core highlight that the mechanism of amyloid formation may share common molecular pathways.
2022-02-28 | PXD006640 | Pride
Project description:Splenic Transitional Type-1 B-cells from CBA wild-type mice, X-linked immunodeficiency mice and Bruton's tyrosine kinase knock-out mice. Two replicates where run on Affymetrix 420 2.0 arrays for CBA wild-type, Xid samples and the Btk KO samples. Bruton's tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important for B-lymphocyte maturation. Mutations in Btk give rise to the primary immunodeficiency disease X-linked agammaglobulinemia (XLA) in man and X-linked immunodeficiency (Xid) in mice. Recent studies have subdivided the mouse immature, or transitional, B-cells into two distinct subsets according to their respective surface markers. Transitional type 1 (T1) and transitional type 2 (T2) cells are also located in distinct anatomic locations. Based on a limited number of markers it has previously been reported that the earliest phenotypic sign of Btk deficiency is manifested at the T2 stage in mice. Here, we report on distinct genome-wide transcriptomic signature differences found in T1 B-lymphocytes from Btk-defective compared to normal mice and demonstrate that Btk deficiency is visible already at this stage. 2 replicates of T1 B-cells from CBA (WT), Xid samples and the Btk KO samples
2014-01-10 | E-GEOD-53946 | biostudies-arrayexpress