RNAseq on APAP, APAP+MSC, APAP+HDF at 24h
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198277 | GEO | 2022/09/16
REPOSITORIES: GEO
Similar Datasets
Project description:Hepatic RNA specimens from mice (C57BL/6) of the 4 groups (vehicle-treated at 24h/48h, n=6; acetaminophen (APAP)-treated (300mg/kg) at 24h/48h, n=7) were pooled at equal shares. Thereafter, pooled RNA underwent analysis by 3'mRNA sequencing (MACE, GenXPro, Frankurt, Germany).
2021-12-31 | GSE169071 | GEO
Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.
2024-04-15 | GSE255777 | GEO
Project description:Overdose of acetaminophen (APAP) is the major cause of acute liver failure in the Western world with very limited treatment options. Previous studies from our groups and others have shown that timely activation of liver regeneration is a critical determinant of transplant-free survival of APAP-induced acute liver failure (ALF) patients. We used affy microarrays to explore the mechanisms of transcriptional expression in YAP-KO mice after 300mg/kg APAP overdose.
2021-10-04 | GSE183119 | GEO
Project description:miRNA profiling of human H9-derived neural stem cells (H9-NSCs) comparing control human adult dermal fibroblasts (hDFs), SOX2-transduced human induced neural stem cells (hDF-iNSC (SOX2)), SOX2/HMGA2-transduced human induced neural stem cells (hDF-iNSC (SOX2/HMGA2)). Goal was to determine the global miRNA expression between the groups. H9-NSC vs hDF vs hDF-iNSC(SOX2) vs hDF-iNSC(SOX2/HMGA2)
2014-07-11 | E-GEOD-59301 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series:; GSE5593: Acetaminophen (APAP) Rat Blood Training Gene Expression Data Set; GSE5594: Acetaminophen (APAP) Rat Blood Test Gene Expression Data Set; GSE5595: Acetaminophen (APAP) Rat Liver Test Gene Expression Data Set; The Supplementary files (appended below) contain the mapping for the decoding of blinded samples. Experiment Overall Design: Refer to individual Series
2008-06-14 | E-GEOD-5652 | biostudies-arrayexpress
Project description:Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, and 3) predicted affected biological pathways. We further demonstrated the implementation of intermediate time points for the identification of early and late response genes. This study illustrated the power of a genome-wide CRISPR-Cas9 screen to systematically identify novel genes involved in APAP-induced hepatotoxicity and to provide potential targets to develop novel therapeutic modalities.
2019-02-04 | GSE112463 | GEO
Project description:The well-known difference in sensitivity of mice and rats to acetaminophen (APAP) liver injury has been related to differences in the fraction that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). Physiologically-based pharmacokinetic modelling was used to identify doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI, to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult.
2023-08-31 | PXD034438 | Pride
Project description:The well-known difference in sensitivity of mice and rats to acetaminophen (APAP) liver injury has been related to differences in the fraction that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). Physiologically-based pharmacokinetic modelling was used to identify doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI, to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult.
2023-06-20 | GSE205201 | GEO
Project description:The well-known difference in sensitivity of mice and rats to acetaminophen (APAP) liver injury has been related to differences in the fraction that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). Physiologically-based pharmacokinetic modelling was used to identify doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI, to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult.
2023-06-20 | GSE205202 | GEO
Project description:To show the similarity among TiPSCs, HDF-iPSCs and ESCs and the differences between TiPSCs and T cells, this experiment was designed. Undifferentiated TiPSCs, HDF-iPSCs and ESCs were collected. And stimulated peripheral circulating terminally differentiated T cells were collected. Then, they were applied in this experiment.
2010-06-16 | E-GEOD-22088 | biostudies-arrayexpress