We compared the gene expression profile from a group of children with T-cell acute lymphoblastic leukamia who remained in continuous complete remission (CCR) (n = 7) with that from a group who relapsed (n = 5), using Affymetrix HG-U133A arrays. Using the decision-tree based supervised learning algorithm Random Forest (RF), genes were ranked with respect to their ability to discriminate between patients who remained in CCR and those who relapsed. From the 300 top-ranked probe sets 9 genes were selected for further investigation and validation in an independent cohort of 25 T-ALL patients using quantitative real time polymerase chain reaction.
Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.
Sex, Age, Specimen part, Disease, Subject
View SamplesLateral root initiation was used as a model system to study the mechanisms behind auxin-induced cell division. Genome-wide transcriptional changes were monitored during the early steps of lateral root initiation. Inclusion of the dominant auxin signaling mutant solitary root1 (slr1) identified genes involved in lateral root initiation that act downstream of the AUX/IAA signaling pathway. Interestingly, key components of the cell cycle machinery were strongly defective in slr1, suggesting a direct link between AUX/IAA signaling and core cell cycle regulation. However, induction of the cell cycle in the mutant background by overexpression of the D-type cyclin (CYCD3;1) was able to trigger complete rounds of cell division in the pericycle that did not result in lateral root formation. Therefore, lateral root initiation can only take place when cell cycle activation is accompanied by cell fate respecification of pericycle cells. The microarray data also yielded evidence for the existence of both negative and positive feedback mechanisms that regulate auxin homeostasis and signal transduction in the pericycle, thereby fine-tuning the process of lateral root initiation.
Cell cycle progression in the pericycle is not sufficient for SOLITARY ROOT/IAA14-mediated lateral root initiation in Arabidopsis thaliana.
No sample metadata fields
View SamplesBackground: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDLs ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathways potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDLs major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-Ideficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
Specimen part
View SamplesCD34+ positively isolated from healthy donors (stimulated by G-CSF) with magnetic beads (after blood leukapheresis)
NA-Seq: a discovery tool for the analysis of chromatin structure and dynamics during differentiation.
No sample metadata fields
View SamplesRNA-seq analysis of human 293 Tet-off cells depleted of PTBP1 and UPF1 alone and in tandem with specific siRNAs. Overall design: siRNA-based depletion of PTBP1, UPF1, and PTBP1/UPF1 together, with a validated non-silencing siRNA as a control.
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.
No sample metadata fields
View SamplesComprehensive analysis of gene expression in hematopoietic stem and progenitor cells from young and old mice.
Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle.
Sex, Age, Specimen part, Time
View SamplesThe number of cells in an organ is a major factor for the determination of organ size. However, genetic basis of cell number determination is not well understood. Three grandifolia-D (gra-D) mutants of Arabidopsis thaliana developed huge leaves containing two- to three-fold increased number of cells of the wild type. Tiling array and microarray analysis of gra-D mutants suggested that genes found in a lower part of chromosome 4 were upregulated, suggesting the occurrence of segmental chromosomal duplications in the gra-D mutants. These region contain positive regulators of cell proliferation such as AINTEGUMENTA (ANT) and cyclin genes such as CYCD3;1.
Impact of segmental chromosomal duplications on leaf size in the grandifolia-D mutants of Arabidopsis thaliana.
Specimen part
View SamplesThe number of cells in an organ is a major factor for the determination of organ size. However, genetic basis of cell number determination is not well understood. Three grandifolia-D (gra-D) mutants of Arabidopsis thaliana developed huge leaves containing two- to three-fold increased number of cells of the wild type. Tiling array and microarray analysis of gra-D mutants suggested that genes found in a lower part of chromosome 4 were upregulated, suggesting the occurrence of segmental chromosomal duplications in the gra-D mutants. These region contain positive regulators of cell proliferation such as AINTEGUMENTA (ANT) and cyclin genes such as CYCD3;1.
Impact of segmental chromosomal duplications on leaf size in the grandifolia-D mutants of Arabidopsis thaliana.
Specimen part
View SamplesBiopsies from uninvolved and from lesional skin of 13 patients with plaque-type psoriasis. Based on paired samples, 179 genes were more than 2-fold differentially expressed in lesional skin.
Increased expression of Wnt5a in psoriatic plaques.
Sex, Age
View SamplesTris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2. We identified that compared to other flame retardants, TCEP and TCIPP had little cytotoxicity. Treatment with sub-cytotoxic concentrations of the two compounds revealed that both chemicals elicited similar effects; both compounds were found to affect genes involved in immune responses and steroid hormone biosynthesis, while also affecting xenobiotic metabolism pathways in a similar manner. Specifically for effects on immune responses, both compounds were shown to alter the expression of the receptor of the potent and pleiotropic complement component, C5a. Additionally, expression of genes encoding for effector proteins involved in the complement cascade along with other potent inflammatory regulators were found altered in response to TCEP and TCIPP, further emphasizing their potential effects on immune function. Taken together, given that TCIPP elicited similar effects compared to TCEP, and at lower concentrations, the potential health effects of TCIPP need to be further studied for a complete risk assessment of the compound. Overall design: HepG2 cells were treated with low (25 uM) or high (250 uM) concentrations of tris(2-chloroethyl) phosphate (TCEP), low (2.5 uM) or high (25 uM) concentrations of tris(2-chloroisopropyl) phosphate (TCIPP). For control purposes, cells were exposed to 0.1% DMSO alone. Treatment lasted for 72 hours. Treatments were done in triplicate for each condition involving separate cell seeding, cell growth, treatments and RNA extractions per triplicate. RNA was isolated with Trizol (Invitrogen, USA) and RNeasy Kit (Qiagen, GER). Libraries were prepared with the TruSeq Stranded mRNA Sample Preparation Kit (Illumina, USA). 50bp long paired-ends reads were sequenced using the HiSeq(R) 1500 platform (Illumina, USA). Alignment, mapping and annotation of sequenced reads were performed using the CLC Genomics Workbench (CLC Bio, Aarhus, Denmark). Samples were normalized by quantile normalization before being mapped and annotated using the human reference hg19 genome.
A toxicogenomics approach to screen chlorinated flame retardants tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate for potential health effects.
Specimen part, Cell line, Treatment, Subject
View Samples