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Mus musculus
15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Canonical Wnt signalling regulates the self-renewal of most if not all stem cell systems. In the blood system, the role of Wnt signalling has been subject of much debate, with positive and negative roles of Wnt signalling proposed for hematopoietic stem cells (HSC). As we have shown previously, this controversy can be largely explained by the effects of different dosages of Wnt signalling. What remained unclear however, was why high Wnt signals would lead to loss of reconstituting capacity. To better understand this phenomenon, we have taken advantage of a series of hypomorphic mutant Apc alleles resulting in a broad range of Wnt dosages in HSCs, purified those HSCs and performed whole genome gene expression analyses. Gene expression profiling and functional studies show that HSCs with APC mutations lead to high Wnt levels , enhanced differentiation and diminished proliferation, but have no effect on apoptosis, collectively leading to loss of stemness. Thus, we provide mechanistic insight into the role of APC mutations and Wnt signalling in HSC biology. As Wnt signals are explored in various in vivo and ex vivo expansion protocols for HSCs, our findings also have clinical ramifications.
Publication Title
High Levels of Canonical Wnt Signaling Lead to Loss of Stemness and Increased Differentiation in Hematopoietic Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Megakaryocytes isolated from Gfi1b flox/flox mice carrying PF4-Cre or not, and from Gfi1b flox/flox mice carrying ROSA-Cre-ERT with or without tamoxifen injection were analyzed for differential expression by RNA-Seq Overall design: A sample of each Gfi1b wild-type and Knock-Out from each model was analyzed
Publication Title
Gfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic stem cells and megakaryocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
These gene expression microarrays were performed as part of a project aiming to integrate quantitative proteomic, gene expression and epigenetic data from the childhood brain tumor medulloblastoma.
Publication Title
Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Human T-cell development is less well studied than its murine counterpart due to the lack of genetic tools and the difficulty of obtaining cells and tissues. However, recent technological advances allow identification of the transcriptional landscape of differentiating human thymocytes. Here we report the gene expression profiles of 11 immature, consecutive T-cell developmental stages. The changes in gene expression of cultured stem cells on OP9-DL1 match those of ex vivo isolated human thymocytes. These analyses led us to define evolutionary conserved gene signatures that represent pre- and post- T-cell commitment stages. We found that loss of CD44 marks T-cell commitment in early CD7+CD5+CD45dim cells, before the acquisition of CD1a surface expression. The CD44-CD1a- post-committed thymocytes have initiated in frame TCR rearrangements and have completely lost the capacity to develop into myeloid, B- and NK-cells, unlike uncommitted CD44+CD1a- thymocytes. Therefore, loss of CD44 represents a previously unrecognized stage that defines the earliest committed T-cell population in the human thymus.
Publication Title
Loss of CD44<sup>dim</sup> Expression from Early Progenitor Cells Marks T-Cell Lineage Commitment in the Human Thymus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Bipolar disorder (BD) is a psychiatric disorder in which the core feature is pathological disturbance in mood ranging from extreme elation (mania) to severe depression. Study has shown an aberrant pro-inflammatory status of monocytes/macrophages in mood disorders. Therefore, this study aimed at studying the monocyte compartment in Bipolar Disorder, by transcription profiling of CD14+ monocytes in patients and controls.
Publication Title
A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1/ mice have previously been characterized and show developmental blocks at the CD4CD8 double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1/ mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1/ mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cellspecific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.
Publication Title
The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. In conclusion, by combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.
Publication Title
Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes
Publication Title
Overexpression of LMO2 causes aberrant human T-Cell development in vivo by three potentially distinct cellular mechanisms.
Sample Metadata Fields
Specimen part
View Samples
GSE18497- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomewide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (stable group), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (skewed group), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication.
Publication Title
Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples