The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago, however its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provides a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell fate decisions, and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice. Overall design: We evaluated the transcriptional profiles of two 53BP1? cell lines and included a positive (WT) and a negative (p53?) controls. These cell lines were treated with Nutlin-3, ionising radiation or mock treated. Three independent replicates were included for each independent condition generating a total of 36 samples.
53BP1 Integrates DNA Repair and p53-Dependent Cell Fate Decisions via Distinct Mechanisms.
Cell line, Treatment, Subject
View SamplesSteer spleen transcriptome
Profile of the Spleen Transcriptome in Beef Steers with Variation in Gain and Feed Intake.
Specimen part
View SamplesWe compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).
Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.
Sex, Age, Specimen part, Disease stage, Race, Subject
View SamplesRNA sequencing (RNA-Seq) was performed on rumen papillae from 16 steers with variation in gain and feed intake. Overall design: Sixteen rumen papillae samples were sequenced by Cofactor Genomics (St.Louis, MO).
Transcriptome differences in the rumen of beef steers with variation in feed intake and gain.
Specimen part, Subject
View SamplesHere we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human-specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17. Key components of the TGF-ß signaling pathway including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1 are also enriched in the human epiblast. Intriguingly, inhibition of TGF-ß signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although key trophectoderm factors Id2, Elf5, and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparisons of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells. Overall design: Single-Cell RNA-seq
Defining the three cell lineages of the human blastocyst by single-cell RNA-seq.
No sample metadata fields
View SamplesU87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, or dibenzazepine (DBZ) when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells.
A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
Specimen part
View SamplesU87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, or dibenzazepine (DBZ), when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells.
A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
Specimen part
View SamplesU87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells.
A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
Cell line
View SamplesMyalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n=14) and matched sedentary controls (n=11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing oxygen consumption (V?O2) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P=0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes. Overall design: RNAseq of whole blood samples from ME/CFS patients and controls following exercise.
Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesWe analysed the translatome and transcriptome of Arabidopsis thaliana Col-0 WT at five distinct physiological states during seed germination.
Extensive translational regulation during seed germination revealed by polysomal profiling.
Specimen part, Time
View Samples