Messenger RNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential it is considered extremely rare in mammals. Here to explore the extent of mRNA retention in metabolic tissues we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single molecule transcript imaging in mouse beta cells, liver and gut. We identify a wide range of protein coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm. These include genes such as the transcription factor ChREBP, Nlrp6, Glucokinase and Glucagon receptor. We demonstrate that nuclear retention of mRNA can efficiently buffer cytoplasmic transcript levels from noise that emanates from transcriptional bursts. Our study challenges the view that transcripts predominantly reside in the cytoplasm and reveals a role of the nucleus in dampening gene expression noise. Overall design: we have total of 8 samples all are mice. liver nuclear RNA (2 replicates), liver cytoplasmic RNA (2 replicates), MIN6 (cell line) nuclear RNA (2 replicates), MIN6 (cell line) cytoplasmic RNA (2 replicates)
Nuclear Retention of mRNA in Mammalian Tissues.
Specimen part, Cell line, Subject
View SamplesNlrp10-deficient mice have a profound defect in helper T cell-driven immune responses. T cell priming is impaired due to a defect in the emigration of a dendritic cells from inflamed tissue and antigen transport to draining lymph nodes. DC chemotaxis to CCR7-dependent and independent ligands is intact in the absence of Nlrp10.
NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells.
Specimen part, Treatment
View SamplesInnate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remain elusive. Here, we use a combination of genome-wide RNA-seq, ChIP-seq and ATAC-seq to compare the transcriptional and epigenetic identity of small intestinal ILCs, identifying thousands of distinct gene profiles and regulatory elements. Single-cell RNA-seq, cytometry, and imaging analyses reveal functional compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes, and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape, and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity. Overall design: ILC1(CD45+CD3-CD19-GR1-B220-CD127+ROR?t-NkP46+), ILC2(CD45+CD3-CD19-GR1-B220-CD127+ROR?t-KLRG1+) and ILC3(CD45+CD3-CD19-GR1-B220-CD127+ROR?t+) were isolated from small intestine lamina propria of WT C57Bl/6 ROR?t-GFP mice, or antibiotics treated mice (vancomycin, ampicillin,kanamycin, and metronidazole)
The Spectrum and Regulatory Landscape of Intestinal Innate Lymphoid Cells Are Shaped by the Microbiome.
Specimen part, Cell line, Treatment, Subject
View SamplesWe report that Klebsiella pneumoniae promote Th1 cell induction in colon. To examine the influence of Klebsiella on colonic epithelial cells (ECs) and lamina propria CD11c+ dendritic cells (DCs), we performed RNA seq on them. Germ free mice were orally inoculated with Kp-2H7 or BAA-2552 and total RNA was isolated from colonic ECs and DCs 1 week after inoculation. Furthermore, we examined the involvement of TLRs in induction of Th1 cells using Myd88 KO, Trif KO, Myd88/Trif DKO mice. These deficient germ free mice were orally inoculated with Kp-2H7 and total RNA was isolated from colonic ECs 3 weeks after inoculation. Overall design: The gene expression of colonic ECs and DCs isolated from germ free mice, and GF mice inoculated with Kp-2H7 or BAA-2552, and colonic ECs isolated from GF Myd88 KO, Trif KO or Myd88/Trif DKO mice inoculated with Kp-2H7.
Ectopic colonization of oral bacteria in the intestine drives T<sub>H</sub>1 cell induction and inflammation.
Specimen part, Cell line, Subject
View SamplesMicroglia play important roles in life-long brain maintenance and in pathology, but are also crucial in the developing central nervous system; yet their regulatory dynamics during development have not been fully elucidated. Genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development reveal that microglia undergo three temporal developmental stages in synchrony with the brain: early, pre-, and adult microglia, which are under the control of distinct regulatory circuits. Knockout of the transcription factor MafB caused disruption of homeostasis in adulthood and increased inflammation. Environmental perturbations, such as the microbiome or prenatal immune activation, led to dysregulation of the developmental program, particularly in terms of inflammation. Together, our work identifies a stepwise developmental program of microglia integrating immune response pathways that may be associated with several neurodevelopmental disorders. Overall design: Yolk sac progenitors (CD45+CD11B+CX3CR1-GFP+), microglia from early brain (CD45+CD11B+CX3CR1-GFP+), and microglia from later stages (CD45intCD11BintCX3CR1-GFP+) were isolated from CX3CR1+ C57BL/6J mice or microglia from perturbation models (CD45intCD11Bint) from mice of C57BL/6J background
Microglia development follows a stepwise program to regulate brain homeostasis.
Specimen part, Cell line, Treatment, Subject
View SamplesComparison of gene expression signatures in undifferentiated hESCs against differentiated embryoid bodies to identify key signatures defining self-renewal of hESCs.
Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.
Specimen part, Cell line
View SamplesWe have performed gene expression microarray analysis to profile transcriptomic signatures affected by EtOH during neural differentiation of human embryonic stem cells
Molecular effect of ethanol during neural differentiation of human embryonic stem cells <i>in vitro.</i>
Specimen part
View SamplesThe aim of this study was to assess the impact of oocyte competence on subsequent fertility. Based on knowledge already accessible in mammals and on bioinformatics tools including the chicken genome sequence, we focused on the expression of genes involved in the processes of fertilization and of early embryo development. The study was performed using two complementary approaches: a descriptive study of standard laying hens and then a differential study performed with hens from experimental lines expressing broad variations of achieved fertility (approximately 20 per cent). A differential kinetic study is performed on INRA lines selected on the basis of their fertility potential in purpose of hopefully access gene markers of fertility performance.
Identification of germinal disk region derived genes potentially involved in hen fertility.
No sample metadata fields
View SamplesBacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) was investigated in six tissues (PBMC, lung, spleen, kidney, heart, Liver).The earliest responses and largest number of affected genes occurred in tissues (PBMCs, spleen and lung) with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Global gene-expression changes measured serially across multiple organs identified new candidate mechanisms of SEB-induced death.
Late multiple organ surge in interferon-regulated target genes characterizes staphylococcal enterotoxin B lethality.
Sex, Specimen part
View SamplesWe report RNA-Seq data of S.cerevisiae PPN1 knock-out yeast strain and PPN1 overproducing transformant yeast strain grown to logarithmic stage in control medium and in the medium containing 5mM manganese. Overall design: Yeast were grown to logarithmic growth stage in control YPD medium and in YPD medium with 5 mM MnSO4.
The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in <i>Saccharomyces cerevisiae</i>.
Cell line, Subject
View Samples