Our data mark GIP as a beneficial immunoregulator during obesity and suggest a novel untapped therapeutic potential for specific targeted GIP analogs.
Glucose-Dependent Insulinotropic Polypeptide Receptor Deficiency Leads to Impaired Bone Marrow Hematopoiesis.
Sex, Specimen part
View SamplesPhytochromes are evolutionarily conserved photoreceptors in bacteria, fungi, and plants. The prototypical phytochrome comprises an N-terminal photosensory module and a C-terminal histidine kinase signaling-output module. However, the plant phytochrome has been postulated to transduce light signals by interacting with a group of nodal Phytochrome-Interacting transcription Factors (PIFs) and triggering their degradation via the N-terminal photosensory module, while its C-terminal output module, including a Histidine Kinase-Related Domain (HKRD), is thought not to participate directly in signaling. Here, we show that the C-terminal module of Arabidopsis phytochrome B (PHYB) is unexpectedly sufficient to mediate the degradation of PIF3 and to induce a distinct set of PIF-regulated photosynthetic genes. These signaling functions require the HKRD and particularly its dimerization. A D1040V mutation, which disrupts the dimerization of HKRD and the interaction between the C-terminal module and PIF3, abrogates the early light signaling functions of PHYB in nuclear accumulation, photobody biogenesis, and PIF3 degradation. In contrast, disruption of the interaction between PIF3 and PHYB's N-terminal photosensory module has little effect on PIF3 degradation. Together, this study provides novel insight into the central mechanism of early phytochrome signaling that the C-terminal signaling-output module of PHYB interacts with PIF3 in the nucleus to mediate PIF3 degradation by light. Overall design: Whole seedling mRNA profiles of 100h dark-grown phyB-9 mutant and BCY overexpression line were generated by deep sequencing, in triplicate, using Illumina NextSeq 500
Mechanism of early light signaling by the carboxy-terminal output module of Arabidopsis phytochrome B.
Subject
View SamplesWe have determined that verticillin A is a histone methyltransfease inhibitor that selectively inhibits human SUV39H1, SUV39H2, G9a and GLP to inhibit H3K9 methylation in human colon cancer cells. The objective here is to identify verticillin A target genes in human colon cancer cells.
H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance.
Cell line, Treatment
View SamplesThe retinoblastoma protein (pRB) is best known for regulating cell proliferation through E2F transcription factors. In this report we investigate the properties of a targeted mutation that disrupts pRB interactions with the transactivation domain of E2Fs. Mice that carry this mutation endogenously (Rb1G) are defective in regulating E2F target genes. Surprisingly, cell cycle regulation in Rb1G/G MEFs strongly resembles that of wild type. In a serum deprivation induced cell cycle exit, Rb1G/G MEFs display a similar magnitude of E2F target gene derepression as Rb1-/-, even though Rb1G/G cells exit the cell cycle normally. Interestingly, cell cycle arrest in Rb1G/G MEFs is responsive to p16 expression, indicating that the G-pRB protein can be activated in G1 to arrest proliferation through non-E2F mechanisms. Some Rb1G/G mice die neonatally with a muscle degeneration phenotype, while the others live a normal lifespan with no evidence of spontaneous tumor formation. Histological analysis reveals discrete examples of hyperplasia in the mammary epithelium, but most tissues appear normal while being accompanied by derepression of pRB regulated E2F targets. This suggests that non-E2F, pRB dependent pathways may have a more relevant role in proliferative control than previously identified.
A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene-targeted mice.
Specimen part
View SamplesWe profiled total mRNA of pancreas and kidney tissues of 3 different strains (p53-null; In4a/Arf-null and WT) of reprogrammable mouse lines (they all express OCT4, SOX2, KLF4, C-MYC under the control of a tetracycline promoter, activated by doxycycline) Overall design: 5 mice of each genotype were treated with doxycycline to induce the expression of the reprogramming factors, they were sacrificed and total mRNA was extracted from pancreas and kidney tissues (we mapped >24M reads per sample)
Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.
Specimen part, Cell line, Subject
View SamplesRNA-seq analysis of BJ cells overexpressing RasV12 and escaping senescence Overall design: Immortalized BJ-hTERT cells expressing an oncogenic version of Ras under the control of a doxycyclin-inducible promoter were grown for 60 days in the presence of Dox to induce oncogene-induced senescence (OIS). Three individual clones escaping senescence were isolated and were analyzed by RNA-seq.
Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner.
Specimen part, Subject
View SamplesWe combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization and “protein-level dependency” studies – a systematic technique that uncovers post-transcriptional regulation – to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs vs. embryonic stem cells (ESCs). Through multiparametric data analyses we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state. Overall design: RNA-seq of Tox4 knockdown in mouse EpiSCs
Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells.
No sample metadata fields
View SamplesThe RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked monogenic disease associating severe learning deficit andassociated to typical facial and digital abnormalities and skeletal changes. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized.
RSK2 is a modulator of craniofacial development.
No sample metadata fields
View SamplesThe goals of this study are to compare transcriptome profiling (RNA-seq) of patients BM with or without ASXL2 mutations. Overall design: Patient bone marrow mRNA profiles with or without ASXL1/2 mutations were generated by deep sequencing
ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia.
Specimen part, Subject
View SamplesThe goals of this study are to compare transcriptome profiling (RNA-seq) of Asxl2 KO LSK cells to that of Asxl2 wild-type cells. We found substantial number of genes are differentially expressed in Asxl2 KO cells. Overall design: LSK mRNA profiles of Asxl2-/- mice and Asxl2wt/wt (WT) were generated by deep sequencing, in triplicate, using Illumina GAIIx.
ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia.
Specimen part, Cell line, Subject, Compound
View Samples