We report differences in mRNA gene expression in rectal biopsies from MSM compared to controls and for MSM timed with episodes of CRAI. Overall design: Rectal biopsies were obtained from MSM at two study timepoints: 1. after who abstaining from CRAI for >72 hours and 2.after engaing in CRAI within the last 24 hours. Rectal biopsies were also obtained from men who never engaged in AI.
Short Communication: Anatomic Site of Sampling and the Rectal Mucosal Microbiota in HIV Negative Men Who Have Sex with Men Engaging in Condomless Receptive Anal Intercourse.
Specimen part, Subject
View SamplesAnalysis of gene expression over serial 150um sections of a single gestational week 14.5 human neocortical specimen. The hypothesis tested with this dataset was that a transcriptional signature of radial glia (neural stem cells) could be isolated via unsupervised gene coexpression analysis due to variation in the abundance of this cell type from section to section. This dataset is the first of its kind generated using this method (Gene Coexpression Analysis of Serial Sections, or GCASS).
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.
Age, Specimen part
View SamplesLYVE-1-positive macrophages were observed to be closely spatially associated with the developing lymphatic vasculature. The role of this population of macrophages in the embryo is uncharacterised.
Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation.
No sample metadata fields
View SamplesRPB1, the largest subunit of RNA polymerase II, contains a highly modifiable C-terminal domain (CTD) that consists of variations of a consensus heptad repeat sequence (Y1S2P3T4S5P6S7). The consensus CTD repeat motif and tandem organization represent the ancestral state of eukaryotic RPB1, but across eukaryotes CTDs show considerable diversity in repeat organization and sequence content. These differences may reflect lineage-specific CTD functions mediated by protein interactions. Mammalian CTDs contain eight non-consensus repeats with a lysine in the seventh position (K7). Posttranslational acetylation of these sites was recently shown to be required for proper polymerase pausing and regulation of two growth factor-regulated genes. To investigate the origins and function of RPB1 CTD acetylation (acRPB1), we computationally reconstructed the evolution of the CTD repeat sequence across eukaryotes and analyzed the evolution and function of genes dysregulated when acRPB1 is disrupted. Modeling the evolutionary dynamics of CTD repeat count and sequence content across diverse eukaryotes revealed an expansion of the CTD in the ancestors of Metazoa. The new CTD repeats introduced the potential for acRPB1 due to the appearance of distal repeats with lysine at position seven. This was followed by a further increase in the number of lysine-containing repeats in developmentally complex clades like Deuterostomia. Mouse genes enriched for acRPB1 occupancy at their promoters and genes with significant expression changes when acRPB1 is disrupted are enriched for several functions, such as growth factor response, gene regulation, cellular adhesion, and vascular development. Genes occupied and regulated by acRPB1 show significant enrichment for evolutionary origins in the early history of eukaryotes through early vertebrates. Our combined functional and evolutionary analyses show that RPB1 CTD acetylation was possible in the early history of animals, and that the K7 content of the CTD expanded in specific developmentally complex metazoan lineages. The functional analysis of genes regulated by acRPB1 highlight functions involved in the origin of and diversification of complex Metazoa. This suggests that acRPB1 may have played a role in the success of animals.
Evolution of lysine acetylation in the RNA polymerase II C-terminal domain.
Cell line
View SamplesPrecursor T-cell lymphoblastic neoplasms are aggressive haematological neoplasm that most often manifest with extensive marrow and blood affectation (T-cell acute lymphoblastic leukaemia or T-ALL) or less commonly as a thymic mass with limited bone marrow infiltration (T-cell lymphoblastic lymphoma or T-LBL). Here we show data from RNA-Seq in a sample series of T-LBL from Spanish patients.The goal was to determine the levels of expression of coding genes and microRNAs, and to identify all genetic variants including SNVs, indels, and fusion transcripts. Overall design: Expression data were determined by comparson of each tumour sample with two control thymuses (404 and 405). Genetic variants were determined by comparison of tumour sequences with canonical ENSEMBL normal-references of each gene.
RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas.
Specimen part, Subject
View SamplesPurpose: To characterize transcriptional changes associated with homozygous inactivation of Dot1l or Mll1 in MN1 driven AML Methods: We sequenced mRNA from murine LSK-cells transformed using forced expression of MN1 (MSCV-MN1-IRES-GFP), and transduced with Cre-vector to inactivate either Dot1l or Mll1. Cells were sorted for Cre-expression (pTomato fluorescent marker) or expression of an inert control vector. Results: Inactivation of either Dot1l or Mll1 in this model leads to a substantial delay or complete abrogation of leukemia development.Loss of Dot1l or Mll1 are associated with gene expression changes that have substantial overlap. In addition, genes that are downregulated follwing inactivation of Dot1l or Mll1 have substantial overlap with the gene set upregulated in MN1 transduced CMPs. Conclusions: MN1 mediated leukemogenesis is associated with a gene expression program that dependes on Mll1 and Dot1l Overall design: Examination of mRNA levels between Dot1l f/f and Dot1l ko, and Mll1 f/f and Mll1 ko.
MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia.
Specimen part, Cell line, Subject
View SamplesPurpose: To characterize transcriptional changes associated with inhibition of Dot1l in 2 inv(16) patient AML samples Methods: We sequenced mRNA from patient samples that were exposed to 5 uM EPZ004777 or DMSO control for 7 days. Results: Inhibition of Dot1l leads to gene expression changes in genes related to cell growth and cell cycle. Overall design: Examination of mRNA levels between cells treated with 5 uM EPZ004777 or DMSO control
MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia.
No sample metadata fields
View SamplesReduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment.
Distinct perturbation of the translatome by the antidiabetic drug metformin.
Cell line, Treatment
View SamplesBy utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.
<i>Dnmt3a</i> restrains mast cell inflammatory responses.
Sex, Specimen part, Treatment
View SamplesWhole blood RNA-seq was leveraged to explore gene expression changes induced in mice 24 hours after immunisation with a second dose of a licensed vaccine against capsular group B meningococcus, one of the vaccines components, or one of several comparator groups. Overall design: mRNA was profiled from RNA extracted from mouse whole blood, 5-6 samples per group, using an Illumina HiSeq4000
Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B meningococcal vaccine, 4CMenB, to the membrane-bound endotoxin of its outer membrane vesicle component.
Sex, Cell line, Subject
View Samples