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SRP158618
Mus musculus
1 Downloadable Sample
NextSeq 500
Description
Gjd3-CreEGFP mice is a novel genetic tool to study the structural and molecular signatures of Atrioventricular Node (AVN) at a high resolution. Overall design: Focusing on the cardiac conduction system, we developed and rigorously characterized a geentic tool Gjd3-CreEGFP to perform in-depth analysis of AVN structure and composition. Utilizing this AVN-specific mouse model, we performed scRNA-Seq on neonatal Gjd3-CreEGFP mice to guide our single-cell atlas of the Atrio-ventricular conduction system (AVCS).
Publication Title
Using Gjd3-CreEGFP mice to examine atrioventricular node morphology and composition.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Published molecular profiling studies in patients with lymphoma suggested the influence of hypoxia inducible factor-1 alpha (HIF1) targets in prognosis of DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We observed that activation of HIF1 resulted in global translation repression during hypoxic stress in DLBCL. Protein translation efficiency as measured using 35S-labeled methionine incorporation revealed a 50% reduction in translation upon activation of HIF1. Importantly, translation was not completely inhibited and expression of clinically correlated hypoxia targets such as GLUT1, HK2, and CYT-C was found to be refractory to translational repression under hypoxia in DLBCL cells. Notably, hypoxic induction of these genes was not observed in normal primary B-cells. Translational repression was coupled with a decrease in mitochondrial function. Screening of primary DLBCL patient samples revealed that expression of HK2, which encodes for the enzyme hexokinase 2, was significantly correlated with DLBCL phenotype. Genetic knockdown studies demonstrated that HK2 is required for promoting growth of DLBCL under hypoxic stress. Altogether, our findings provide strong support for the direct contribution of HK2 in B-cell lymphoma development and suggest that HK2 is a key metabolic driver of the DLBCL phenotype.ne incorporation revealed a 50% reduction in translation upon activation of HIF1. Importantly, translation was not completely blunted and expression of clinically correlated hypoxia targets such as GLUT1, HK2, and CYT-C was found to be refractory to translational repression under hypoxia in DLBCL cells. Notably, hypoxic induction of these genes was not observed in normal primary B-cells. Translational repression was coupled with decrease in mitochondrial function. Screening of DLBCL patient samples identified that expression of HK2, which encodes for the enzyme hexokinase 2, was significantly correlated with DLBCL phenotype. Genetic knockdown studies show that HK2 is required for promoting growth of DLBCL under hypoxic stress. Altogether, our findings provide more definitive proof of direct contribution of HK2 in development of B-cell lymphoma and suggest that HK2 is a key metabolic driver of DLBCL phenotype.
Publication Title
Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
We analysed the transcriptional signature in endothelial cells extracted from the bone marrow of mice engrafted with human AML and compared it to the one of mice engrafted with human normal hematopoietic cells Overall design: Immunodeficient mice were transplanted with human AML cells derived from patients, or with normal human hematopoietic cells derived from cord blood. Mice were sacrificed once assessed the bone marrow engraftment, and the bones were processed to isolate endothelial cells using the CD31 marker. RNA was extracted, sequencing libraries were prepared and sequenced.
Publication Title
Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a lethal complication of cancer treatment. Although t-MDS/AML development is associated with known genotoxic exposures, its pathogenesis is not well understood and methods to predict risk of development of t-MDS/AML in individual cancer survivors are not available. We performed microarray analysis of gene expression in samples from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) and controls that did not develop t-MDS/AML after aHCT. CD34+ progenitor cells from peripheral blood stem cell (PBSC) samples obtained pre-aHCT from t-MDS/AML cases and matched controls, and bone marrow (BM) samples obtained at time of development of t-MDS/AML, were studied. Significant differences in gene expression were seen in PBSC obtained pre-aHCT from patients who subsequently developed t-MDS/AML compared to controls. Genetic alterations in pre-aHCT samples were related to mitochondrial function, protein synthesis, metabolic regulation and hematopoietic regulation. Progression to overt t-MDS/AML was associated with additional alterations in DNA repair and DNA-damage checkpoint genes. Altered gene expression in PBSC samples were validated in an independent group of patients. An optimal 63-gene PBSC classifier derived from the training set accurately distinguished patients who did or did not develop t-MDS/AML in the independent test set. These results indicate that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and can accurately identify those at risk of developing this complication.
Publication Title
Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study was performed to understand the gene expression changes that accompany treatment of renal cell carcinoma (RCC) with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Human RCC cell lines were implanted into the flanks of nude beige mice, allowed to reach 12mm in long axis, and then treated with TKIs (sunitinib or sorafenib). Tumors were excised at 2 timepoints (prior to any therapy and at the 20mm endpoint of the study) and gene expression analysis was performed.
Publication Title
Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is somewhat paradoxical that proliferator gamma coactivator 1-alpha (PGC1a), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here we report that PGC1a's induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1a knockout tubular cells were sensitized to the genotoxic stressor cisplatin whereas transgenic cells were protected. The biosensor mtKeima unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1a not only counteracted this effect but also raised basal mitophagy, as did the downstream mediator nicotinamide adenine dinucleotide (NAD+). PGC1a did not consistent affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1a in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1a's exquisite reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a novel target for renal tubular stress resistance. Overall design: 12 samples in total = 3 replicates each from 4 groups
Publication Title
TFEB-driven lysosomal biogenesis is pivotal for PGC1α-dependent renal stress resistance.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ZBTB20 is an adjuvant-specific factor for long-term antibody responses. This factor is critical for maintaining long-lived plasma cells in alum-adjuvanted antibody responses but is dispensable for TLR ligand-adjuvanted responses.
Publication Title
Adjuvant-specific regulation of long-term antibody responses by ZBTB20.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 4000
Description
Lgr6-positive cells have been shown to label stem/progenitors cells in several tissues including tongue and skin. However their role in mammary gland has never been investigated. Here we used Lgr6-eGFP-IRES-CreER2 mice to isolate and characterize Lgr6-positive population in mammary gland of 5-week old female mice. Overall design: Examination of transcriptional differences between Lgr6 positive and negative cells
Publication Title
Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Oryza sativa
- 12 Downloadable Samples
- Affymetrix Rice (US) Gene 1.0 ST Array (rusgene10st)
Description
Several homeobox genes belonging to HD-ZIP I subfamily are highly induced by drought stress at various developmental stages in rice. To analyze the role of a candidate HD-ZIP I subfamily member, OsHOX24, we constitutively overexpressed it in rice. The physiological analyses revealed that overexpression of OsHOX24 gene reduced drought stress tolerance in transgenic plants as compared to wild-type.
Publication Title
Over-Expression of <i>OsHOX24</i> Confers Enhanced Susceptibility to Abiotic Stresses in Transgenic Rice via Modulating Stress-Responsive Gene Expression.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Clade A PP2C Highly ABA-Induced1 (HAI1, At5g59220) is strongly up-regulated by low water potential in an ABA-dependent manner. Using knockout mutants of hai1, we found that HAI1 functions as a negative regulator of low water potential-induced proline and osmoregulatory solute accumulation. We also found a relatively weak and limited interaction of HAI1 with the RCAR/PYL family of ABA receptors. This, plus its induced expression, suggest that HAI1 remains active during stress and attenuates specific aspects of drought response.
Publication Title
Unique drought resistance functions of the highly ABA-induced clade A protein phosphatase 2Cs.
Sample Metadata Fields
Specimen part, Treatment
View Samples