This SuperSeries is composed of the SubSeries listed below.
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Specimen part, Cell line
View SamplesHomologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities. Here, we identified an HRD gene signature that robustly predicted HRD status. Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK. We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map. Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information.
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Specimen part, Cell line
View SamplesHomologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities. Here, we identified an HRD gene signature that robustly predicted HRD status. Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK. We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map. Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information.
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Specimen part, Cell line
View SamplesHomologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities Here, we identified an HRD gene signature that robustly predicted HRD status Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Specimen part, Cell line
View SamplesInduced pluripotent stem cells (iPSCs) have been generated from various somatic cells under feeder-layer conditions. These feeder-derived iPSCs generated in different labs exhibit greater variability than between different traditional embryo derived hESC lines. For that reason, it is important to develop a standard and defined system for deriving autologous patient stem cells. We have generated iPSCs under feeder-free conditions using Matrigel coated vessels in chemically defined medium, mTeSR1. These feeder-free derived iPSCs are in many ways similar to feeder-derived iPSCs and also to hESCs, with respect to their pluripotent gene expression (OCT4, NANOG, SOX2), protein expression (OCT4, NANOG, SSEA4, TRA160) and differentiation capabilities.
Human induced pluripotent stem cells derived under feeder-free conditions display unique cell cycle and DNA replication gene profiles.
Specimen part
View SamplesIn recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum ?–secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions. Overall design: 6 samples were analyzed, 3 replicates of ETOH treated H1 HESCs and 3 replicates of DAPT treated H1 HESCs
Transcriptional profiling of ectoderm specification to keratinocyte fate in human embryonic stem cells.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma.
Disease
View SamplesGene expression profiling of extranodal nasal-type NK/T cell lymphoma and other EBV-associated lymphoid proliferation disease patients was analyzed to elucidate association between JAK-STAT pathway and canonical or non-canonical PRC2/EZH2 target pathways using Illumina HumanRef-8 v3 chips.
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma.
Disease
View SamplesThe siRNA transfection includes JAK3 and EZH2 siRNAs. The plasmid transfection includes EZH2 WT and its mutants.
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma.
Cell line
View SamplesGene expression profiling of extranodal nasal-type NK/T cell lymphoma and other EBV-associated lymphoid proliferation disease patients was analyzed to elucidate association between JAK-STAT pathway and canonical or non-canonical PRC2/EZH2 target pathways using Illumina HumanRef-8 v3 chips.
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma.
Disease
View Samples