In this study we investigated to which extend aberrant c Myc activity plays a functional role in other aNHL and whether it is independent from MYC translocations. Based on a combined microarray analysis of human germinal centre (GC) B cells transfected with c Myc and 220 aNHLs cases, we developed a c Myc index.
High Myc activity is an independent negative prognostic factor for diffuse large B cell lymphomas.
Specimen part, Treatment
View SamplesGene expression was compared between four B-cell derived HL cell lines (L428, L1236, L591, KMH2) and GC B cells from three different patients.
The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype.
No sample metadata fields
View SamplesIn this study, we have investigated the effect of LMP1 on gene expression in normal human GC B cells using a non-viral vector based system
The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype.
No sample metadata fields
View SamplesThis study presents a dynamic characterization of the sheep milk transcriptome aiming at achieving a better understanding of the sheep lactating mammary gland. Transcriptome sequencing (RNA-seq) was performed on total RNA extracted from milk somatic cells from ewes on days 10, 50, 120 and 150 after lambing. The experiment was performed in Spanish Churra and Assaf breeds, which differ in their milk production traits. Nearly 67% of the annotated genes in the reference genome (Oar_v3.1) were expressed in ovine milk somatic cells. For the two breeds and across the four lactation stages studied, the most highly expressed genes encoded caseins and whey proteins. We detected differentially expressed genes (DEGs) across lactation points, with the largest differences being found, between day 10 and day 150. Upregulated GO terms at late lactation stages were linked mainly to developmental processes linked to extracellular matrix remodeling. A total of 256 annotated DEGs were detected in the Assaf and Churra comparison. Some genes selectively upregulated in the Churra breed grouped under the endopeptidase and channel activity GO terms. These genes could be related to the higher cheese yield of this breed. Overall, this study provides the first integrated overview on sheep milk gene expression. Overall design: A total of eight healthy sheep were selected to be included in the experiment, four Assaf and four Churra ewes. 32 Milk Somatic Cells (MSCs) samples were collected on days 10, 50, 120 and 150 after lambing. In each time point 4 biological replicates from each breed were collected unless on day 120 that only three biological replicates from each breed were sequenced.
Variant discovery in the sheep milk transcriptome using RNA sequencing.
Specimen part, Subject
View SamplesWe previously found that the SF3A mRNA splicing complex was required for a robust innate immune response; SF3A acts in part by inhibiting the production of a negatively acting splice form of the TLR signaling adaptor MyD88. Here we inhibit SF3A1 using RNAi and subsequently perform an RNAseq study to identify the full complement of genes and splicing events regulated by SF3A in murine macrophages. Surprisingly, SF3A has substantial specificity for mRNA splicing events in innate immune signaling pathways compared to other pathways, affecting the splicing of many genes in the TLR signaling pathway to modulate the innate immune response. Overall design: RNAseq was used to monitor the effects of SF3A1 siRNA-mediated knockdown in murine macrophages. Three biological replicates were used for each of the four treatment combinations (with/without siRNA, with/without LPS). The first replicates for each combination were each sequenced in two runs, which were combined in the analysis.
Regulation of toll-like receptor signaling by the SF3a mRNA splicing complex.
No sample metadata fields
View SamplesMesenchymal stem cells (MSCs) And osteolineage cells contribute to the hematopoietic stem cell (HSC) Niche in the bone marrow of long bones. However, Their developmental relationships remain unclear. Here we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin- MSCs participate in fetal skeletogenesis, And lose MSC activity soon after birth. In contrast, Quiescent neural-crest-derived nestin+ Cells in the same bones preserve MSC activity, But do not generate fetal chondrocytes. Instead, They differentiate into HSC-niche-forming MSCs, Helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ PDGFR- Cell population also contains Schwann-cell precursors, But does not comprise mature Schwann cells. Thus, In the developing bone marrow HSC-niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, And ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation. Overall design: Total RNA was isolated from small numbers of FACS sorted stromal cells, obtained from neonatal Nes-Gfp bone marrow preparations (2 biological replicates). Each independent set of samples was obtained from pooled skeletal elements (long bones and sterna) form multiple littermates.
The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.
No sample metadata fields
View SamplesPrevious studies have reported that the tumour cells of nasopharyngeal carcinoma (NPC) exhibit both recurrent chromosome abnormalities and changes in the expression of numerous genes. However, it is not known to what extent changes in the copy number of individual genes are associated with the observed expression changes. To address this, a genome wide analysis of chromosome copy number and gene expression was performed in tumour cells micro-dissected from the same NPC biopsies. Significant gene expression changes were identified in tumour suppressor genes (TSGs) and in tumour-promoting genes (TPGs) but almost 60% of these can be either upregulated or downregulated in different types of cancer. This suggests that the simplistic classification of genes as TSGs or TPGs may not be entirely appropriate and that the concept of onco-suppressors may be more extensive than previously recognised. Several genomic regions showing frequent copy number gain or loss were identified. Whereas TSGs were significantly enriched within regions of frequent loss, no significant enrichment of TPGs was observed in regions of frequent gain. However, on a gene by gene basis little correlation was found between DNA copy number and alterations in gene expression except for loss of expression from homozygous deletions and a single highly amplified segment which showed enhanced gene expression.
A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels.
Disease, Disease stage
View SamplesNasopharyngeal carcinoma (NPC) is a common cancer in southern China and South East Asia where more than 50,000 new cases are diagnosed each year.
The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma.
Disease, Disease stage
View SamplesEstrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced myeloproliferative neoplasm in vivo, and sensitized MLL-AF9+ leukemias to chemotherapy. Tamoxifen showed selective effects on mutant cells compared to normal ones, and had only a minor impact on steady-state hematopoiesis in disease-free animals. These results uncover specific regulation of hematopoietic progenitors by estrogens and potential anti-leukemic properties of SERM Overall design: LT-HSCs, ST-HSCs and MPPs sorted from the bone marrow of mice treated with tamoxifen or vehicle (3 biological replicates per group)
Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis.
No sample metadata fields
View SamplesDiffuse large B-cell lymphoma (DLBCL) has striking clinical and molecular variability. Although a more precise identification of the multiple determinants of this variability is still under investigation, there is a consensus that high-clinical-risk DLBCL cases require a risk-adapted therapy, since intensification of chemotherapy with autologous stem-cell transplantation (ASCT) has been shown to improve the prognosis for high-risk patients in randomised clinical trials.
Identification of biological markers of sensitivity to high-clinical-risk-adapted therapy for patients with diffuse large B-cell lymphoma.
No sample metadata fields
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