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SRP165725
Homo sapiens
27 Downloadable Samples
Illumina HiSeq 4000
Description
CD19-specific CARs that comprise CD28 and CD3z signaling domains program highly performing effector functions that mediate potent tumor elimination, but they impart a relatively limited T cell lifespan. Increasing functional T cell persistence without reducing effector potency is therefore likely to further enhance the therapeutic success of 1928z CAR T cells. We demonstrate that the number and position of ITAMs in 1928z CAR T cells influence functional, phenotypic and transcriptional programs, resulting in profound effects on antitumor efficacy. Improved therapeutic potency of CAR T cells can thus be achieved by calibrating activation strength, thereby retaining memory functions and preventing exhaustion, without compromising effector functions. Our transcriptional analysis underscores the potential of ITAM dosage and position to direct different T cell fates. We were able to identify a novel CAR design, termed 1XX, which programs a favorable balance of effector and memory signatures, inducing increased persistence of highly functional CARs with the replicative capacity of long-lived memory cells and potent effector functions. Overall design: In order to assess the different phenotypic and functional patterns of CARs encoding a single immunoreceptor tyrosine-based activation motif (ITAM), we compared the genome-wide transcriptional profiles of 1928z, 1XX and XX3 after CD19 antigen stimulation of TRAC-edited naïve T cells. Sorted naïve (TN), stem cell memory (TSCM) and effector (TEFF) CD8+ T cells served as controls.
Publication Title
Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
We show that NRF2 activation drives hepatocellular carcinoma development in vivo. Moreover, NRF2 undergoes glucose dependent modification called glycation and requires the de-glycating enzyme FN3K to maintain NRF2' oncogenic functions. Overall design: Gene expression analysis in MYC-driven murine HCC with and without NRF2 activation. NRF2 is activated by targeting its negative regulators Keap1 or Cul3 or targeting NRF2 ETGE motif by sgRNA/Cas9 editing.
Publication Title
The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demonstrated that a dominant mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrheic dermatitis. We defined ZNF750 as a nuclear effector that is strongly activated in and essential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differentiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier
Publication Title
ZNF750 is expressed in differentiated keratinocytes and regulates epidermal late differentiation genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Targeted interference of sin3a-tgif1 function by SID decoy treatment inhibits WNT signaling and invasion in triple negative breast cancer cells. MDA-MB-231 cells were treated with scrambled SID control, 2.5M SID peptide or untreated for 24h.
Publication Title
Targeted interference of SIN3A-TGIF1 function by SID decoy treatment inhibits Wnt signaling and invasion in triple negative breast cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Of the members of mitochondrial transcription termination factors (mTERFs) found in metazoans and plants known to regulate organellar gene expression at various levels, plant mTERF6 promotes maturation of a tRNA
Publication Title
Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 89 Downloadable Samples
- Illumina HiSeq 2500
Description
We developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof-of-principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both shRNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons. Overall design: We tried to idenitify transcripitional profiles and specific transcription factors that involved in of different stages during hypothalamic neuron differentiation from single cell sequencing for hESC-derived Day27 hypothalamic neurons, Day 12 neuron progenitors and undifferentiated stem cells
Publication Title
PC1/3 Deficiency Impacts Pro-opiomelanocortin Processing in Human Embryonic Stem Cell-Derived Hypothalamic Neurons.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is unknown if gene expression profiles from primary RCC tumors differ from patient-matched metastatic tumors. Thus, we sought to identify differentially expressed genes between patient-matched primary and metastatic RCC tumors in order to understand the molecular mechanisms underlying the development of RCC metastases.
Publication Title
Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer.
Publication Title
Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Rationale: The Id1 and Id3 genes play major roles during cardiac development, despite their expression being confined to non-myocardial layers (endocardium endothelium - epicardium). We previously described that Id1/Id3/ double knockout (dKO) mouse embryos die at mid-gestation from multiple cardiac defects, but early demise precluded the studies of the roles of Id in the adult mice.
Publication Title
Developmental ablation of Id1 and Id3 genes in the vasculature leads to postnatal cardiac phenotypes.
Sample Metadata Fields
Age, Specimen part
View Samples