Self-cleaving guide RNAs enable pharmacological selection of precise gene editing events in vivo
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216550 | GEO | 2022/10/25
REPOSITORIES: GEO
Similar Datasets
Project description:In metabolic control, GC signaling acts as a major counter-regulatory system against insulin action, and aberrantly elevated GC activity is tightly linked to major components of the so-called Metabolic Syndrome, including obesity, insulin resistance, hyperglycemia, and systemic dyslipidemia. Here we identify the hepatic induction of the conserved microRNA (miR)-379/410 genomic cluster as a key component of GC/GR-driven metabolic dysfunction in M-bM-^@M-^\diabesityM-bM-^@M-^] Microarray data were utilized to screened for differentially regulated miRNAs between wt and db/db and between wt and GR Knockdown mice For wt vs. db/db: mice were fasted for 24 hours and refed for 6 hours; For GR-dependent miRNAs: mice were treated with rAAV delivering either control or GR-directed miRNA for the knockdown of the GR specifically in the liver.
2014-10-15 | E-GEOD-55245 | biostudies-arrayexpress
Project description:Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 axis have made a breakthrough in the treatment of non-small cell lung cancer (NSCLC). However, a paradoxical boost in tumor growth was reported in a fraction of NSCLC patients after ICIs administration: a novel pattern of cancer progression defined “hyperprogressive disease” (HPD). Because the mechanism of HPD onset has not completely elucidated yet, this study aimed at investigating the cellular and molecular bases of this clinical phenomenon. Pre-treatment histological samples obtained from NSCLC patients were evaluated by immunohistochemistry (IHC) for immune cell infiltrate. Tissue samples from all patients with HPD showed tumor-infiltration by M2-like macrophages. To validate these findings in preclinical models, we utilized athymic nude mice that, lacking T-cells that may cloud the results, represent a suitable model to evaluate the role of macrophages in determining HPD. Immunodeficient mice were injected with human NSCLC NCI-H460 cell line, treated with anti-PD-1 antibody and tumor growth was evaluated over time. Anti-PD-1 treated H460 tumor-bearing mice showed HPD-like tumor growth as well as an increase in macrophage infiltration compared to control group. Interestingly, in these in vivo models, HPD-like growth, triggered by anti-PD-1 treatment, was dependent of anti-PD-1 antibody Fc domain. These results suggest that macrophages are the major players in HPD development and that FcR engagement on macrophages may determine a functional reprogramming of these immune cells toward a more aggressive and pro-tumorigenic phenotype, eventually inducing HPD.
2023-01-11 | GSE210547 | GEO
Project description:The goal of this study was to evaluate the role of HDAC4 in spinal sensitization. We analyzed gene expression changes associated with the subcellular localization of HDAC4 in the spinal cord dorsal horn following CFA-induced inflammatory pain. The analysis was performed in basal conditions and after intraplantar injection of CFA to the hind paw of mice that received intraspinal injection of rAAV-constructs influencing the subcellular localization of HDAC4.
2021-12-31 | GSE159895 | GEO
Project description:We performed transcriptomic profiling of mouse whole liver cells perfused in situ with collagenase and then mechanically dissociated into single cell suspensions, to garner about 40% hepatocytes and 60% non-parenchymal cells. Cells were isolated from male and female C57BL/6J mice that received either PBS vehicle control, or 400 mg/kg acetaminophen (APAP) and perfused 48 hours after injury.
2023-12-01 | GSE206782 | GEO
Project description:Hyperprogressive disease (HPD) is a newly described pattern of tumor progression characterizing a percentage of cancer patients receiving an immunotherapeutic regimen based on immune checkpoint inhibitors (ICIs), such as anti-PD1/PDL1 antibodies. Patients experiencing HPD are characterized by an unpredictable acceleration of tumor growth and a deterioration of the clinical conditions, rapidly leading to death. We have previously reported that macrophages play a pivotal role in contributing to HPD development. By analyzing non-small cell lung cancer (NSCLC) patient tumor samples, we observed that the tumor microenvironment (TME) of HPD-patients was infiltrated by particular clusters of macrophages. These macrophages are present before the initiation of ICI therapy and, therefore, we hypothesized that certain tumor cells may induce the acquisition of an “HPD-related” phenotype in macrophages that upon interaction with anti-PD1 antibody can unleash HPD. Since one of the strategies exploited by cancer cells to educate macrophage is to secrete molecules with immunomodulatory activity in the TME, bone marrow-derived macrophages (BMDMs) were exposed for 24 hours to the conditioned medium (CMs) obtained from five different NSCLC cell lines. We found that macrophages exposed to the CMs obtained from NCI-H460 and PC9 cell lines, reported to undergo a HPD-like growth in immunocompromised mice after anti-PD1 antibody treatment, have a gene expression profile completely different compared to the other experimental groups. Our findings suggest that soluble factors released by tumor cells can reprogram macrophages towards a phenotype potentially able to trigger HPD after interaction with anti-PD1 antibody.
2023-01-11 | GSE210340 | GEO
Project description:Self-cleaving guide RNAs enable pharmacological selection of precise gene editing events in vivo
| PRJNA894207 | ENA
Project description:Male C57BL6/N mice were obtained from Janvier Labs (France). Mice were starved overnight before APAP administration and were fed ad libitum afterward. A single dose of 300 mg APAP/kg b.w. was intraperitoneally injected in warm phosphate-buffered saline (PBS; Table 3). The used APAP was obtained from Sigma-Aldrich (A7085-500G, Germany). The mice were sacrificed at 1, 6, and 12 hours, and on days 1, 2, 4, 6, and 8 after APAP administration. Expression data of the livers of male C57Bl6/N mice after intoxication with paracetamol (APAP)
2021-06-30 | GSE167032 | GEO
Project description:CRISPR adaptive immune systems protect bacteria from infections by deploying CRISPR RNA (crRNA)-guided enzymes to recognize and cut foreign nucleic acids. Type VI-A CRISPR-Cas systems include the Cas13a enzyme, an RNA-activated RNase capable of crRNA processing and single-stranded RNA degradation upon target-transcript binding. Here we present the 2.0-Å resolution crystal structure of a crRNA-bound Lachnospiraceae bacterium Cas13a (LbaCas13a), representing a recently discovered Cas13a enzyme subtype. This structure and accompanying biochemical experiments define the Cas13a catalytic residues that are directly responsible for crRNA maturation. In addition, the orientation of the foreign-derived target-RNA-specifying sequence in the protein interior explains the conformational gating of Cas13a nuclease activation. These results describe how Cas13a enzymes generate functional crRNAs and how catalytic activity is blocked before target-RNA recognition, with implications for both bacterial immunity and diagnostic applications.
| S-EPMC5961731 | biostudies-literature
Project description:Understanding the function of individual miRNA species in mice would require the production of hundreds of loss-of-function strains. To accelerate analysis of miRNA biology in mammals, we combined recombinant adeno-associated virus (rAAV) vectors with miRNA ‘Tough Decoys’ (TuDs) to inhibit specific miRNAs. Intravenous injection of rAAV9 expressing anti-miR-122 or anti-let-7 TuD depleted the corresponding miRNA and increased its mRNA targets. rAAV producing anti-miR-122—but not anti-let-7—TuD reduced serum cholesterol by 40% for 18 weeks in wild-type mice and reduced serum LDL by 50% in LDL receptor-deficient mice. High throughput sequencing of liver miRNAs from the treated mice confirmed that the targeted miRNA, but no other miRNAs, were depleted and revealed that TuD RNAs induce miRNA tailing and trimming in vivo. rAAV-mediated miRNA inhibition thus provides a simple way to study miRNA function in adult mammals and a potential therapy for dyslipidemia and other diseases caused by miRNA deregulation. Examining the effect of Tough Decoy miRNA inhibitors on miRNA stability and integrity
2011-12-10 | E-GEOD-25971 | biostudies-arrayexpress
Project description:In this study, human particulated dentin (HPD) was developed. The characteristic of HPD was examinated by XRD, EDX and cytotoxicity test. HPD was used to implant in the calvarial defects of New Zealand White rabbits. bone tissue and blood samples were taken at 3, 5 and 7 days post-implantation for microarray experiment. The gene expression profiles and signaling pathways were monitored using GeneSpring software and Ingenuity Pathways Analysis (IPA), respectively. We used microarray and IPA to elucidate the global programme of gene expression and identified distinct classes of up- and down- regulated genes during HPD treated healing process.
2016-06-21 | GSE83553 | GEO