Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell RNA-sequencing analysis of human hepatic organoids derived from human induced pluripotent stem cells

ABSTRACT: Liver is a central organ for drug and xenobiotics metabolism in human body. Due to the differences in interspecies metabolism, human model system for liver metabolism is necessary. However, the hepatic model systems derived from human pluripotent stem cells for metabolic screening and assays did not recapitulate the most of metabolic capabilities of human liver or primary human hepatocytes to date. In this study, we developed human hepatic endoderm organoids which are expandable and subsequently differentiated human hepatic organoids having metabolic capabilities. To investigate the cellular composition and properties of human hepatic organoids in single cell level, we performed single cell RNA-sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153019 | GEO | 2023/06/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA-sequencing analysis of human hepatic organoids derived from human induced pluripotent stem cells

Project description:Liver is a central organ for drug and xenobiotics metabolism in human body. Due to the differences in interspecies metabolism, human model system for liver metabolism is necessary. However, the hepatic model systems derived from human pluripotent stem cells for metabolic screening and assays did not recapitulate the most of metabolic capabilities of human liver or primary human hepatocytes to date. In this study, we developed human hepatic endoderm organoids which are expandable and subsequently differentiated human hepatic organoids having metabolic capabilities. To investigate the transcriptome of human hepatic organoids, we performed RNA-sequencing.

2023-06-22 | GSE155458 | GEO

Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bio-activation and detoxification

Project description:Hepatic organoids are a recent innovation in in vitro modelling. Initial studies suggest organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their propensity for drug metabolism and detoxification remains poorly characterised. A global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was therefore performed to assess both their similarity to liver tissue and DMET expression. iTRAQ analysis revealed 4,405 proteins commonly detected across all sample types. Differentiation of organoids significantly increased the expression of multiple CYP450s, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, they contain multiple DMET proteins necessary for liver function and drug metabolism, such as CYP450 3A, GSTA and MDR1A. Hepatic organoids may therefore represent an attractive novel model for hepatotoxicity testing, although further experimentation, optimisation and characterisation is needed relative to pre-existing models to fully contextualise their use as a putative in vitro model of DILI.

2021-06-03 | PXD017986 | Pride

Gene expression profiles in human liver organoid-derived hepatocytes

Project description:Human liver organoids are expected to be a hepatocyte source for preclinical in vitro studies. Although these organoids show long-term proliferation, their hepatic functions remain low. Here, we propose a novel method for two dimensional (2D)-cultured hepatic differentiation from human liver organoids. When cultured under a 2D condition, the single cells from human liver organoids were seeded on collagen type I-coated plates. Then, optimal conditions for hepatic differentiation were screened using several reagents. We determined the 2D-cultured hepatocyte differentiation method from human liver organoids. Hepatic gene expressions in human liver organoids-derived hepatocytes (Org-HEPs) were greatly increased, compared to those in human liver organoids. The metabolic activities of cytochrome P450 (CYP) 1A2, CYP2C8, CYP2E1 and CYP3A4 were at levels comparable to those in primary human hepatocytes (PHHs). These results suggested that human liver organoids could be differentiated into highly functional hepatocytes in 2D culture. We also treated Org-HEPs and PHHs with hepatotoxic drugs. The cell viability of Org-HEPs was almost the same as that of PHHs, suggesting that Org-HEPs could be used for hepatotoxicity tests. Thus, Org-HEPs will be useful for pharmaceutical research.

2024-08-29 | GSE234459 | GEO

Human Embryonic Stem Cell-derived Expandable Hepatic Organoids Enable Pathophysiological Model of Alcoholic Liver Injury

Project description:Human Embryonic Stem Cell-derived Expandable Hepatic Organoids Enable Pathophysiological Model of Alcoholic Liver Injury

| PRJNA528629 | ENA

Generation and characterization of mature hepatocyte organoids for liver metabolic studies

Project description:The liver plays a central role in whole body metabolic regulation. Studies of liver metabolism are mostly done in vivo in animal models due to the lack of reliable in vitro systems that can recapitulate liver metabolic functions and their regulation. Hepatocyte organoids (HOs) generated in vitro recently are powerful tools for liver regeneration. Here we developed a novel culture condition that enabled successful generation of mature hepatocyte organoids (MHOs) with metabolic functions characteristic of adult livers. We showed that the MHOs can be used to study gene expression that exhibit zonal patterns in vivo, hepatic proliferation during tumorigenesis and metabolic alterations in disorders of both alcoholic and non-alcoholic fatty liver diseases.

2024-05-15 | GSE245632 | GEO

Subtherapeutic antibiotics alter the murine colonic microbiome and early life adiposity

Project description:Early life exposure to antibiotics alters the gut microbiome. These alterations lead to changes in metabolic homeostasis and an increase in host adiposity. We used microarrays to identify metabolic genes that may be up- or down-regulated secondary to antibiotic exposure. Low dose antibiotics have been widely used as growth promoters in the agricultural industry since the 1950’s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we hypothesized that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy (STAT) to young mice and evaluated changes in the composition and capabilities of the gut microbiome. STAT administration increased adiposity in young mice and altered hormones related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids (SCFA), increases in colonic SCFA levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early life murine metabolic homeostasis through antibiotic manipulation. C57BL6 mice were divided into low-dose penicillin or control groups. Given antibiotics via drinking water after weaning. Sacrificed and liver sections collected for RNA extraction.

2012-06-30 | E-GEOD-38880 | biostudies-arrayexpress

Panel-based next-generation sequencing study of human liver samples.

Project description:Panel-based next-generation sequencing study of 150 human surgical liver samples from Caucasian donors with detailed medical documentation. The overall purpose of the study was to identify expression quantitative trait loci (eQTL) in human liver for genes involved in absorption, distribution, metabolism and excretion of drugs, other xenobiotics, and endogenous substances.

| EGAS00001003426 | EGA

Human Embryonic Stem Cell-derived Expandable Hepatic Organoids Enable Pathophysiological Model of Alcoholic Liver Injury

Project description:We report the generation of human pluripotent-stem-cell-derived (hPSC), expandable hepatic organoids (hEHOs) using a newly established method that consists of subjecting hPSCs to a sequence of distinct wholly defined (serum-free, feeder free) media lineage restricting the cells to become determined hepatic stem cells followed by a process of shifting the cells from monolayer (2D) to organoid (3D ) cultures. The hEHOs stably keep phenotypic features of a bi-potent hepatic lineage that can differentiate into functional hepatocytes or cholangiocytes. The hEHOs can expand for over 20 passages enabling industrial scaling to amounts requisite for industry or clinical programs. The cells from culture are able to engraft rapidly into injured liver parenchyma of FRG mice following transplantation and to differentiate in vivo into mature hepatocytes. If implanted into the epididymis fat pads of immune-deficiency mice, they do not generate non-hepatic lineages nor teratomas. We further developed a derivative model by incorporating human fetal liver mesenchymal cells (hFLMCs) into the hEHOs, referred as hFLMC/hEHO, and used the organoids to model alcohol liver disease-associated pathophysiologic changes, such as oxidative stress generation, steatosis, inflammatory mediators release and fibrosis, following treatment with alcohol. Our work demonstrates that the hFLMC/hEHO provide a novel ex vivo pathophysiological model for studying alcohol liver disease as well as many other non-genetic liver diseases.

2020-03-01 | GSE128717 | GEO

Self-assembled Matrigel-free iPSC-derived liver organoids demonstrate wide-ranging highly-differentiated liver functions

Project description:Investigate the functional capabilities of human iPSC-derived liver organoids generated on Matrigel or self-assembed in rotating wall vessel (RWV) via bulk RNA-seq, RT-qPCR and immunostaining, to provide a simple and high-throughput way to generate Matrigel-free liver organoids for research and clinical applications

2023-03-08 | GSE222273 | GEO

Raw data for manuscript : "Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD"

Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one third of the global population. Understanding metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative stress, enhancing acute hepatotoxicity. Glycine supplementation or hepatocyte-specific ablation of the mitochondrial SHMT2 isoform in mice with hepatic steatosis mitigated acetaminophen-induced hepatotoxicity by supporting de novo glutathione synthesis. Thus, early metabolic changes in MASLD that limit glycine availability sensitize mice to xenobiotics even at the reversible stage of this disease.

2023-12-12 | MSV000093653 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data