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SRP119425
Homo sapiens
2 Downloadable Samples
Illumina HiSeq 2500
Description
We report changes in B cells in patients treated with combination immune checkpoint blockade (CCB; anti-CTLA4 and anti-PD1) Overall design: We examine CD19+ sorted B cells before and after CCB therapy
Publication Title
Early B cell changes predict autoimmunity following combination immune checkpoint blockade.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.
Publication Title
Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression in murine ES cells
Publication Title
Modeling insertional mutagenesis using gene length and expression in murine embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The distribution of genomic variations in human iPSCs is related to replication-timing reorganization during reprogramming.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cell fate change involves significant genome reorganization, including change in replication timing, but how these changes are related to genetic variation has not been examined. To study how change in replication timing that occurs during reprogramming impacts the copy number variation (CNV) landscape, we generated genome-wide replication timing profiles of induced pluripotent stem cells (iPSCs) and their parental fibroblasts. A significant portion of the genome changes replication timing as a result of reprogramming, indicative of overall genome reorganization. We found that early and late replicating domains in iPSCs are differentially affected by copy number gains and losses, and that in particular CNV gains accumulate in regions of the genome that change to earlier replication during the reprogramming process. This differential relationship was present irrespective of reprogramming method. Overall, our findings reveal a functional association between reorganization of replication timing and the CNV landscape that emerges during reprogramming.
Publication Title
The distribution of genomic variations in human iPSCs is related to replication-timing reorganization during reprogramming.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
LMO2 regulates gene expression facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the Germinal Center (GC) reaction and is expressed in GC-derived non-Hodgkins lymphomas. LMO2 is one of the most powerful prognostic indicators in DLBCL patients. However, its function in GC B cells and DLBCL is currently unknown. In the present study we characterized the LMO2 transcriptome and interactome in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners such as LDB1, E2A, HEB, Lyl1, ETO2 and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, NFATc1 and LEF-1 proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF-1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provide a platform for future elucidation of LMO2 function in GC B-cells and DLBCL pathogenesis.
Publication Title
Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.
Publication Title
Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 318 Downloadable Samples
- Illumina HiSeq 2500
Description
Differentiation of human pluripotent stem cells toward definitive endoderm (DE) is the critical first step for generating cells comprising organs such as the gut, liver, pancreas and lung. This in-vitro differentiation process generates a heterogeneous population with a proportion of cells failing to differentiate properly and maintaining expression of pluripotency factors such as Oct4. RNA-sequencing of single cells collected at four time points during a 4-day DE differentiation identified high expression of metallothionein genes in the residual Oct4-positive cells that failed to differentiate to DE. Using X-ray fluorescence microscopy and multi-isotope mass spectrometry, we discovered that high intracellular zinc level corresponds with persistent Oct4 expression and failure to differentiate. We further show that differentiation-arrested phenotype is inversely correlated with zinc concentration in the differentiation media. This study improves our understanding of in-vitro DE differentiation and provides actionable options to improve DE differentiation efficiency. Overall design: RNA-sequencing of 329 single cells collected at four time points during a 4-day DE differentiation to identify mechanisms leading to cellular heterogeneity during differentiation
Publication Title
Single-cell RNA sequencing reveals metallothionein heterogeneity during hESC differentiation to definitive endoderm.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Gprc6a|Mck-/- (Gcrp6a skeletal muscle specific knockout)(n=4) are compared to Gprc6afl/fl (WT) mice (n=4). Gprc6a is the osteocalcin receptor. Overall design: Gprc6a/Mck-/- vs Gprc6afl/fl
Publication Title
Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
IL-21 induces B cell activation, and differentiation into antibody-secreting plasmablasts in vitro. This process is abolished by loss-of function mutations in STAT3
Publication Title
IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts.
Sample Metadata Fields
Specimen part, Disease
View Samples