A NAFLD Model Created By Endoplasmic Reticulum Stress Response-Associated Steatosis in Human Induced Pluripotent Stem Cell-Derived Hepatocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA477582 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:cdipt is an essential gene in the synthesis of phosphatidylinositol (PtdIns) in the zebrafish, Danio rerio. The zebrafish mutant cdipt^hi559Tg (ZL782) carries a retroviral insertion which inactivates cdipt. Homozygous mutants exhibit hepatocellular endoplasmic reticulum (ER) stress and non-alcoholic fatty liver disease (NAFLD) pathologies at 5 days post fertilization (dpf). This study reveals a novel link between PtdIns, ER stress, and steatosis. We compared whole animal gene expression profiles of hi559 mutant larvae with phenotypically wild type larvae from a heterozygote incross in triplicate.
2011-05-09 | E-GEOD-17711 | biostudies-arrayexpress
Project description:cdipt is an essential gene in the synthesis of phosphatidylinositol (PtdIns) in the zebrafish, Danio rerio. The zebrafish mutant cdipt^hi559Tg (ZL782) carries a retroviral insertion which inactivates cdipt. Homozygous mutants exhibit hepatocellular endoplasmic reticulum (ER) stress and non-alcoholic fatty liver disease (NAFLD) pathologies at 5 days post fertilization (dpf). This study reveals a novel link between PtdIns, ER stress, and steatosis.
2011-05-09 | GSE17711 | GEO
Project description:Our study reports a phenotypic approach to model hepatic steatosis in induced pluripotent stem cell-derived hepatocytes
2018-09-13 | GSE116185 | GEO
Project description:Melatonin has been reported to improve NAFLD, exploring the underlying mechanisms will be beneficial for better treatment of NAFLD. CDHFD- and MCD-fed mice with melatonin intervention exhibited significantly decreased liver steatosis, lobular inflammation, and focal liver necrosis. Single-cell RNA sequencing revealed melatonin selectively inhibited proinflammatory CCR3+ MoMFs, and upregulated anti-inflammatory CD206+ MoMFs in NAFLD mice. Hepatic infiltrated CCR3+CD14+ MoMFs is also significantly increased in patients with NAFLD. Mechanistically, melatonin receptor independent BTG2-ATF4 signaling plays a vital role in the regulation of CCR3+ MoMFs endoplasmic reticulum stress, survival, and proinflammation by melatonin. In contrast, melatonin upregulated CD206+ MoMFs survival and polarization via MT1/2 receptors. Melatonin stimulation also regulates human CCR3+ MoMFs and CD206+ MoMFs survival and inflammation in vitro. Furthermore, CCR3 depletion antibody monotherapy decreased liver inflammation and improved NAFLD in mice. Thus, Therapies targeting CCR3+ MoMFs may have potential benefits in NAFLD treatment.
2023-06-04 | GSE204821 | GEO
Project description:In eukaryotic cells, the spatial regulation of protein expression is frequently conferred through the coupling of mRNA localization and the local control of translation. mRNA localization to the endoplasmic reticulum (ER) is a prominent example of such regulation and serves a ubiquitous role in segregating the synthesis of secretory and integral membrane proteins to the ER. Recent genomic and biochemical studies have now expanded this view to suggest a role for the ER in global protein synthesis. We have utilized cell fractionation and ribosome profiling to obtain a genomic survey of the subcellular organization of mRNA translation and report that ribosomal loading of mRNAs, a proxy for mRNA translation, is biased to the ER. Notably, ER-associated mRNAs encoding both cytosolic and topogenic signal-encoding proteins display similar ribosome loading densities, suggesting that ER-associated ribosomes serve a global role in mRNA translation. We propose that the partitioning of mRNAs and their translation between the cytosol and ER compartments may represent a novel mechanism for the post-transcriptional regulation of gene expression. HEK293 cells were fractionated between the cytosol and endoplasmic reticulum. Within each fraction, ribosome footprints were generated and sequenced. In parallel, total mRNA was sequenced.
2011-12-20 | E-GEOD-31539 | biostudies-arrayexpress
Project description:Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the involvement of PTMs in ketogenic diet (KD)-improved fatty liver by multi-omics and reveal a core target of lysine malonylation, acetyl-CoA carboxylase 1 (ACC1). ACC1 protein levels and Lys1523 malonylation are significantly decreased by KD. It is discovered that a malonylation-mimic mutant in ACC1 increases its enzyme activity and stability to promote hepatic steatosis, whereas the malonylation-null mutant upregulates the ubiquitination degradation of ACC1. A customized Lys1523ACC1 malonylation antibody confirms the increased malonylation of ACC1 in the NAFLD samples. Overall, the lysine malonylation of ACC1 is attenuated by KD in NAFLD and plays an important role in promoting hepatic steatosis. Malonylation is critical for ACC1 activity and stability, highlighting the anti-malonylation effect of ACC1 as a potential strategy for treating NAFLD.
2023-07-21 | PXD040481 | Pride
Project description:Latent pancreatic cancer metastases are created when T cells select disseminated cancer cells in which immune resistance and quiescence have been imposed by endoplasmic stress
2018-01-06 | GSE108811 | GEO
Project description:In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.
2016-11-30 | GSE85686 | GEO
Project description:We obtained transcriptional profiles of third instar eye imaginal disc nuclei with or without endoplasmic reticulum stress using next generation sequencing (NGS). We employed an isolation of nuclei tagged in specific cell type (INTACT) protocol (Ma and Weake, J. of Vis. Exp., 2014) to label nuclear membranes of GMR-GAL4-expressing cells with EGFP. The experimental group also expressed a mutant allele of the membrane visual protein rhodopsin (Rh-1(G69D)), which is known to cause endoplasmic reticulum stress and initiate Unfolded Protein Response (UPR) signaling. The goal of this study was to characterize the transcriptional changes associated with endoplasmic reticulum stress responses in a commonly used platform, the eye imaginal disc.
2021-09-20 | GSE150058 | GEO
Project description:Mutations in the p53 tumor suppressor gene are the most frequent genetic alteration in cancer and often associated with progression from benign to invasive, metastatic stages. Mutations inactivate tumor suppression by p53 and endow the protein with novel gain-of-function (GOF) activities that actively promote tumor progression, metastasis and therapy resistance. By comparative gene expression profiling of p53-mutated and p53-depleted cancer cells we identified ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) as a mutant p53 (mutp53) target gene. A comprehensive pan-cancer analysis revealed a highly significant correlation between GOF p53 mutations and elevated expression of ENTPD5. Mechanistically, regulation of ENTPD5 by mutp53 is mediated by the histone H3 lysine 4 (H3K4) methyltransferase COMPASS complex. ENTPD5 has been shown to function in the endoplasmic reticulum as a UDPase to promote the N-glycosylation and folding of membrane proteins such as growth factor receptors and integrins. We show ENTPD5 to be a mediator of mutp53 GOF activity in clonogenic growth, architectural tissue remodeling, migration, invasion, and lung colonization in an experimental metastasis mouse model. Our study reveals N-glycosylation in the endoplasmic reticulum as a novel mechanism underlying the progression of tumors with mutp53 that could provide new possibilities for treating cancers driven by GOF p53 mutations.
2016-11-29 | E-MTAB-4672 | biostudies-arrayexpress