PD-1 immune checkpoint blockade provides significant clinical benefits for cancer patients. However, factors influencing innate sensitivity remain incompletely catalogued. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies. Mutations in cell adhesion genes and the DNA repair gene BRCA2 were enriched in responding tumors, and a high mutational load associated with improved survival. Innately resistant tumors displayed frequent transcriptomic up-expression of genes that enriched for mesenchymal transition, cell adhesion, ECM organization, wound-healing and angiogenesis. The transcriptomes of innate resistance also enriched for signatures indicating up-regulation of these processes. Notably, MAPK-targeted therapy (MAPKi) induced similar signatures in melanoma, suggesting that a form of MAPKi resistance mediates cross-resistance to anti-PD-1 therapy. Co-enrichment of IPRIM (Innate anti-PD-1 Resistance Induced by MAPKi) signatures defined a transcriptomic subset across advanced cancers, suggesting that attenuating processes underlying these signatures may augment anti-PD1 responses. Thus, multi-factorial determinants influence anti-PD-1 patterns in melanoma. Overall design: Melanoma biopsies pre-anti-PD-1 therapy were sent for transcriptomic analysis by paired-end RNAseq analysis to find the correlates of response vs. non-response to the therapy
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.
No sample metadata fields
View Samples-myosin heavy chain promoter controlled MerCreMer expression enables conditional, cardiomyocyte specific and tamoxifen dependent gene inactivation of floxed genes. Administration of tamoxifen has been linked to development of acute and transient cardiomyopathy. The mechanism for this is unknown.
Cre-loxP DNA recombination is possible with only minimal unspecific transcriptional changes and without cardiomyopathy in Tg(alphaMHC-MerCreMer) mice.
Sex, Specimen part, Time
View SamplesBMP treatment induces expression of late differenitation genes in primary human keratinocytes. Overall design: RNA-seq analysis after treatment with EGFR inhibitor AG1478 with or without BMP27 or BMP inhibitor DMH1. each treatment and control was performed in triplicate
Single-Cell ID-seq Reveals Dynamic BMP Pathway Activation Upstream of the MAF/MAFB-Program in Epidermal Differentiation.
Specimen part, Subject
View SamplesWe report the effects of silencing SRSF1 or ZMAT2 in human epidermal stem cells on the transcriptome of epidermal stem cells. We found that silencing ZMAT2 or SRSF1 affects global splicing, however, ZMAT2 seems to regulate splicing of a smaller more specific subset of genes. Overall design: RNA-sequencing data following silencing SRSF1 or ZMAT2
Splicing and Chromatin Factors Jointly Regulate Epidermal Differentiation.
Specimen part, Subject, Time
View SamplesWe report the effects of induction of differentiation in human epidermal stem cells on the splicing of the transcriptome. Overall design: RNA-sequencing data following induction of differentiation in human epidermal stem cells
Splicing and Chromatin Factors Jointly Regulate Epidermal Differentiation.
Specimen part, Treatment, Subject
View SamplesPerinatal asphyxia is detrimental to the newborn baby and the use of supplemental oxygen during resuscitation may worsen the prognosis of these babies. The mechanism behind hyperoxic injury is not fully understood and our aim was to investigate four oxygen therapies following hypoxia and these effects on transcriptional activity.
Transcriptome profiling of the newborn mouse brain after hypoxia-reoxygenation: hyperoxic reoxygenation induces inflammatory and energy failure responsive genes.
Specimen part
View SamplesWe developed an affinity purification approach to isolate tagged nuclei in mice (similar to INTACT; [Deal R.B. and Henikoff S. A simple method for gene expression and chromatin profiling of individual cell types within a tissue. Dev. Cell 18,1030-1040. (2010)]) and used it to characterize genome-wide patterns of transcription, DNA methylation, and chromatin accessibility in 3 major neuron classes of the neocortex (excitatory pyramidal neurons, parvalbumin (PV)-positive GABAergic interneurons, and vasoactive intestinal peptide (VIP)-positive GABAergic interneurons). By combining cell purification and integrative analysis, our findings relate the phenotypic and functional complexity of neocortical neurons to their underlying transcriptional and epigenetic diversity. Overall design: RNA-seq, MethylC-seq, ATAC-seq, and ChIP-seq for histone modifications using INTACT-purified nuclei from the mouse neocortex
Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain.
No sample metadata fields
View SamplesHere we characterized the transcriptome and epigenome of control keratinocytes during differentiation. Epigenomic analyses showed that the temporal enrichment of p63 motifs in dynamic enhancers underscores the key role of p63 in orchestrating the enhancer landscape during keratinocyte differentiation. The cooperation between p63 and its co-regulating factors, such as RUNX1, is important for the finetuning of gene expression. Overall design: RNA-Seq, H3K4me3 ChIP-Seq and H3K27me3 ChIP-Seq of keratinocytes during differentiation on day0(proliferation), day2(early differentiation), day4(mid differentiation) and day7(late differentiation). RUNX1 ChIP-Seq of keratinocytes at the proliferation stage(day0).
Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.
No sample metadata fields
View SamplesUndifferentiated and differentiated Keratinocytes (AG1478 treated) were stained with antibody-RNA conjugates to measure protein-based diffrentiation changes in conjunction with single-cell transcriptomics. The cells were crosslinked and stained according to the RAID procedure to allow intracellular immunostaining. Antibodies used in this experiment are (TGM1, NOTCH1, KLK6, JAG1, phospho-RPS6, phospho-FAK). Overall design: Three 384 wells plates for untreated and Three 384 wells plates for AG1478 treated cells were processed for single cell transcriptomics
Combined quantification of intracellular (phospho-)proteins and transcriptomics from fixed single cells.
Specimen part, Treatment, Subject
View SamplesCell fixation, permeabilization and antibody staining of could have adverse effects on the quality of single cell transcriptomics data. To assess the effects of the RAID procedure, which includes such steps, we performed a direct comparison of single cell transcriptomics by CELseq2 using unfixed and RAID-processed cells. Quality measures (gene complexity, gene detection rate, average gene expression) were performed using 40000 samples UMI counts per cell. Overall design: Single cells were sorted in 96, wells plates. Per condition (unfixed or RAID) three sets (A,B,C) of 48 cells were processed with the CELseq2 protocol.
Combined quantification of intracellular (phospho-)proteins and transcriptomics from fixed single cells.
Specimen part, Subject
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