Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2203450_1.fastq.gz | Fastqsanger.gz | |||
| ERR2203450_2.fastq.gz | Fastqsanger.gz | |||
| ERR2203451_1.fastq.gz | Fastqsanger.gz | |||
| ERR2203451_2.fastq.gz | Fastqsanger.gz | |||
| ERR2203452_1.fastq.gz | Fastqsanger.gz |
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Project description:Background and aims: The initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD) is challenging to study in vivo in humans and robust in vitro high-fidelity disease models are limited. Although primary human hepatocytes (PHH) are often considered to be the gold-standard, immortalized hepatic cell lines are often utilised because of their scalability and experimental tractability. Therefore, the aim of this study was to compare the metabolic responses of PHHs with our characterized Huh7-based model when exposed to the physiologically-relevant fatty acid (FA) mixtures. Methods: PHH and Huh7 cells were treated with 2% human serum and a combination of sugar and FAs enriched in either unsaturated (OPLA) or saturated (POLA) FAs for 4 or 7 days, respectively. Stable isotope tracers were utilized to investigate basal changes in hepatocyte metabolism in response to different treatment regimes. Changes in cell viability, media biochemistry, intracellular metabolism, lipid droplet morphology and gene expression were quantified. Results: Huh7 cells had greater viability than PHH, while NEFA uptake and triglyceride secretion were similar. Both OPLA and POLA increased the proportion of large lipid droplets in Huh7 cells, whereas only OPLA produced comparable effects in PHH. Despite higher baseline TG in PHH, both models showed similar lipid composition, de novo lipogenic responses, and glycogen levels. Compared to Huh7 cells PHH exhibited higher media 3-hydroxybutyrate, lower media lactate, reduced glucose uptake, and donor-dependent transcriptomic variability. Conclusions: Our data demonstrate that Huh7 cells are metabolically adaptable and when cultured in physiologically relevant media metabolic readouts are more similar to those observed in PHH cells, thus making Huh7 a potentially useful workhorse model to investigate relevant pathways that may underpin the development of MASLD.
2026-07-08 | GSE334407 | GEO
Project description:HepaRG 3D baseline samples
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Project description:Imatinib is a tyrosine kinase inhibitor (TKI) indicated for chronic myeloid leukemia (CML) and other cancers. It is metabolized by CYP2C8 and CYP3A into a major active metabolite N-desmethyl-imatinib. The purpose of the study was to determine in vitro the influence of CYP2C8 and CYP3A phenotypes, such as protein concentration and activity, and genotypes on imatinib clearance and N-desmethyl imatinib formation. Individual-donor and pooled human liver microsomes (HLM) and primary human hepatocytes (PHH) were incubated with imatinib to determine the rate of clearance of imatinib and formation of N-desmethyl-imatinib. HLMs were also investigated to determine their CYP2C8 and CYP3A activity and protein concentrations. Results were compared to evaluate the relationship between the CYP phenotypes and imatinib clearance and N-desmethyl-imatinib formation. For PHH samples, CYP2C8, CYP3A4, and CYP3A5 genotypes were also determined and imatinib metabolism was compared between the genotype groups. CYP3A5 metabolizer phenotype groups were also used to compare CYP phenotypes and imatinib metabolism in the PHH samples. The CYP targeted proteomics concentration measurements for the HLMs were undertaken on a nanoLC-QTRAP 5500 system (SCIEX mass spectrometer, Framingham, MA, USA) and the PHH measurements were determined on a microLC-Triple quadrupole 7500 system (also SCIEX mass spectrometer). Unlike the HLMs, membrane protein was extracted from the PHH samples before being trypsin digested. The data showed that, in HLM donors, CYP3A activity was the most significant predictor of imatinib clearance while CYP2C8 activity was the most significant predictor of N-desmethyl-imatinib formation. Additionally, in PHH, imatinib clearance was more significantly correlated with CYP2C8 phenotypes than CYP3A phenotypes. There was a significant difference in imatinib clearance between CYP2C8*1/*1 individuals and CYP2C8*3 carriers in PHH donors. Overall, the results support previous work that CYP2C8 plays a key role in imatinib metabolism and could provide insight into interindividual variability seen in patients taking the medication.
2025-12-13 | PXD066482 | Pride
Project description:Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain’s ventricles followed by excessive accumulation of cerebrospinal fluid (CSF) leading to ventricular enlargement and increased intracranial pressure. However, the precise mechanisms driving PHH development and persistence remain incompletely known and lack medical and disease modifying treatments. Here we use a mouse model of PHH to identify transcriptomic, proteomic and cellular changes involving neurovascular and neuroimmunological microglial alterations as features of PHH, overlapping with those reported in human disease. Improvements on a lysophosphatidic acid (LPA)-initiated PHH mouse model were developed and combined with unbiased proteomic and single-nucleus transcriptomics that identified microglial molecular pathways promoting PHH. Pharmacological disruption of microglia in vivo significantly reduced PHH-associated ventriculomegaly. These data identify microglia and neurovascular molecular elements in the development of PHH, implicating them as potentially tractable therapeutic targets towards developing new treatments for PHH.
2025-05-22 | GSE272062 | GEO
Project description:PBEC Baseline samples from Leiden
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Project description:hu-PCLS baseline samples from ITEM
| PRJEB24489 | ENA