This SuperSeries is composed of the SubSeries listed below.
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Age, Specimen part, Cell line, Treatment
View SamplesAmplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Cell line, Treatment
View SamplesAmplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. Using a MYC target gene signature that predicts poor neuroblastoma prognosis we identified the histone chaperone, FAcilitates Chromatin Transcription (FACT), as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small molecule Curaxin compound, CBL0137, markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with chemotherapy in standard use by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN amplified neuroblastoma cells and a treatment strategy for MYCN-driven neuroblastoma
Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy.
Specimen part
View SamplesOur goal was to transcriptionally profile Prdm1+ cell lineages of maternal and embryonic origin in mid-gestation mouse placenta in order to study vascular mimicry and additional processes in the placenta. Overall design: Profiling of 61 single cells and 17 clusters of 2 or 3 cells chosen based on expression of Prdm1, a paternally inherited Prdm1-Venus fluorescent reporter, progenitor trophoblast marker Gjb3 and spiral artery trophoblast giant cell marker Prl7b1.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy.
Specimen part, Cell line, Subject
View SamplesExpression profiling of wild-type and Prdm1 null mouse trophoblast giant cell cultures using Illumina whole genome mouse V2 arrays.
Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming.
Specimen part
View SamplesEpiblast cells in the early post-implantation stage mammalian embryo undergo a transition described as lineage priming before cell fate allocation, but signaling pathways acting upstream remain ill defined. Genetic studies demonstrate that Smad2/3 double-mutant mouse embryos die shortly after implantation. To learn more about the molecular disturbances underlying this abrupt failure, here we characterised Smad2/3-deificient embryonic stem cells (ESCs). We found that Smad2/3 double-knockout ESCs induced to form epiblast-like cells (EpiLCs) display changes in nave and primed pluripotency marker gene expression, associated with the disruption of Oct4-bound distal regulatory element. In the absence of Smad2/3, we observed enhanced Bmp target gene expression and de-repression of extra-embryonic gene expression. Cell fate allocation into all three embryonic germ lakers is disrupted. Collectively, these experiments demonstrate that combinatorial Smad2/3 functional activities are required to maintain distinct embryonic and/or extra-embryonic cell identity during lineage priming in the epiblast before gastrulation.
Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lhx1 functions together with Otx2, Foxa2, and Ldb1 to govern anterior mesendoderm, node, and midline development.
Specimen part
View SamplesExpression profiling of wild-type and Lhx1 null mouse definitive endoderm cultures using Illumina whole genome mouse V2 arrays.
Lhx1 functions together with Otx2, Foxa2, and Ldb1 to govern anterior mesendoderm, node, and midline development.
Specimen part
View Samples