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GSE33031
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To guarantee blood supply throughout adult life hematopoietic stem cells (HSCs) need to carefully balance between self-renewing cell divisions and quiescence. Identification of genes controlling HSC self-renewal is of utmost importance given that HSCs are the only stem cells with broad clinical applications. Transcription factor PU.1 is one of the major regulators of myeloid and lymphoid development. Recent reports suggest that PU.1 mediates its functions via gradual expression level changes rather than binary on/off states. So far, this has not been considered in any study of HSCs and thus, PU.1s role in HSC function has remained largely unclear. Here we demonstrate using hypomorphic mice with an engineered disruption of an autoregulatory feedback loop that decreased PU.1 levels resulted in loss of key HSC functions, all of which could be fully rescued by restoration of proper PU.1 levels via a human PU.1 transgene. Mechanistically, we found excessive HSC cell divisions and altered expression of cell cycle regulators whose promoter regions were bound by PU.1 in normal HSCs. Adequate PU.1 levels were maintained by a mechanism of direct autoregulation restricted to HSCs through a physical interaction of a -14kb enhancer with the proximal promoter. Our findings identify PU.1 as novel regulator controling the switch between cell division and quiescence in order to prevent exhaustion of HSCs. Given that even moderate level changes greatly impact stem cell function, our data suggest important therapeutic implications for leukemic patients with reduced PU.1 levels. Moreover, we provide first proof, that autoregulation of a transcription factor, PU.1, has a crucial function in vivo. We anticipate that our concept of how autoregulation forms an active chromosomal conformation will impact future research on transcription factor networks regulating stem cell fate.
Publication Title
Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Analysis of early changes in the R-H model of carcinogenesis in order to investigate the relationship between oval cell proliferation and preneoplastic foci
Publication Title
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 13 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Analysis of early changes in the R-H model of carcinogenesis in order to investigate the relationship between oval cell proliferation and preneoplastic foci
Publication Title
Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion.
Publication Title
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thalidomide-dexamethasone (TD) combination is an effective induction therapy for newly diagnosed multiple myeloma patients, candidates for subsequent autologous stem cell transplantation (ASCT). Since maximization of tumor response before ASCT may favorably affect the clinical outcomes, we designed a study to identify a gene expression profile (GEP) signature predictive of attainment of complete response to TD induction therapy. CD138+ bone marrow samples obtained at diagnosis from 112/311 patients were analyzed. Two subsequent time phases were planned. Firstly, a GEP supervised analysis, performed on a training set of 32 patients, allowed to identify 157 probe sets differentially expressed in complete responder + near complete responder (CR+nCR) versus partial responder patients. Than, we generated an 8-gene GEP signature predicting at diagnosis the probability to achieve CR+nCR to TD induction therapy. The performance of this assay was subsequently validated in an 80 patients training set. The 8-gene signature provide a negative predictive value of 93% and a positive predictive value of 44%. The 8 genes were down-regulated in patients who achieved at least a nCR. These results could be an important first step to adopting a diagnostic assay, used to determine, at diagnosis, patients who will respond more favourably to a particular treatment strategy.
Publication Title
Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide-dexamethasone incorporated into double autologous transplantation.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Pseudomonas aeruginosa
- 29 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
To better understand the role of QscR in P. aeruginosa gene regulation and to better understand the relationship between QscR, LasR and RhlR control of gene expression we used transcription profiling to identify a QscR-dependent regulon. Our analysis revealed that QscR activates some genes and represses others. Some of the repressed genes are not regulated by the LasR-I or RhlR-I systems while others are. The LasI-generated 3-oxododecanoyl-homoserine lactone serves as a signal molecule for QscR. Thus QscR appears to be an integral component of the P. aeruginosa quorum sensing circuitry. QscR uses the LasI-generated acyl-homoserine lactone signal and controls a specific regulon that overlaps with the already overlapping LasR and RhlR-dependent regulons.
Publication Title
A distinct QscR regulon in the Pseudomonas aeruginosa quorum-sensing circuit.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 173 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Identifying the genes underlying quantitative trait loci (QTL) for disease has proven difficult, mainly due to the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals and test candidate genes. In addition to identifying the causative genes, defining the pathways that are affected by these QTL is of major importance as it can give us insight into the disease process and provide evidence to support candidate genes. In this study we mapped three significant and one suggestive QTL on Chromosomes (Chrs) 1, 4, 15, and 17, respectively, for increased albumin excretion (measured as albumin-to-creatinine ratio) in a cross between the MRL/MpJ and SM/J mouse inbred strains. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL. Among these were the glycan degradation, leukocyte migration, and antigen presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL, but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease.
Publication Title
Uncovering genes and regulatory pathways related to urinary albumin excretion.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 29 Downloadable Samples
Illumina HiScanSQ, Illumina HiSeq 2500
Description
Naive spleens as well as naive and LPS-treated dendritic cells from wildtype and GPR34-/- mice were sequenced to integrate expression profiles with protein interaction networks and find functional modules that are affected by GPR34 Overall design: Expression profiles of dendritic cells and whole spleens were generated using Illumina HiSeq 2500/ Illumina HiScan
Publication Title
Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived normal human kidney transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis Overall design: The kidney tissue was immediately placed and stored in RNAlater® (Ambion), according to the manufacturer’s instruction. The tissue was manually microdissected under microscope in RNAlater® pool for glomerular and tubular compartment. Dissected tissue was homogenized and RNA was prepared using RNAeasy mini columns (Qiagen, Valencia, CA, US), according to the manufacturer’s instructions. RNA quality and quantity were determined using the Laboratory-on-Chip Total RNA PicoKit Agilent BioAnalyzer. Only samples without evidence of degradation were further used (RNA Integrity Number >6).
Publication Title
Functional genomic annotation of genetic risk loci highlights inflammation and epithelial biology networks in CKD.
Sample Metadata Fields
No sample metadata fields
View Samples