Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiles in human liver organoid-derived hepatocytes

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234459 | GEO | 2024/08/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [FigS3]

Project description:Although aging associated decline of liver regeneration was discovered half a century ago, how aging contributes to the decline of liver regenerative capacity and how to improve this capacity in the elderly is still unknown. Hepatocyte plasticity is known to play a central role in the maintenance of liver regeneration; hence, we describe a strategy to explore the mechanisms underlying the relation between aging and hepatocyte plasticity: experiments with human induced-pluripotent-stem-cell–derived hepatocytes (hiPSC-Heps). Here, we established a simple and convenient method for generation of hiPSC-Heps that can maintain hepatic function for a long time with gradual accumulation of aging related markers and characteristics. We found that in contrast to rodent hepatocytes, FGF2 is essential for the plasticity of human hepatocytes, and the FGF2-activated MAPK–EZH2 axis can help to reprogram hiPSC-Heps into proliferative hepatic cells with a bipotential differentiation ability. Notably, our results showed the plasticity of hiPSC-Heps decreases with aging and this phenomenon strongly correlates with histone acetylation. Moreover, we found that selective inhibition of histone deacetylases can markedly improve the plasticity of old hiPSC-Heps and primary human hepatocytes and surprisingly increases the repopulation capacity of old PHHs in a liver injury model. Therefore, we can conclude that aging-associated histone hypoacetylation impairs hepatocyte plasticity.

2022-03-04 | GSE131805 | GEO

Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [Fig4]

2022-03-04 | GSE131803 | GEO

Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [Fig1, FigS1 and Fig3]

2022-03-04 | GSE131802 | GEO

Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells

Project description:The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.

2021-04-20 | GSE128060 | GEO

Gene expression profiles of HYDROX-cultured human liver organoids compared to those of Matrigel-cultured human liver organoids.

Project description:Human liver organoids, an in vitro 3D culture system to recapitulate biological tissue, are expected to be used for drug discovery. However, Matrigel, the most widely used extracellular matrix for organoid culture, has concerns about safety and reproducibility since it is murine-derived. Morever, low hepatic functions of human liver organoids compared to primary human hepatocytes is considered a challenge. Herein, we attempted to culture human liver organoids, established from primary (cryopreserved) human hepatocytes (PHH), using HYDROX, a chemically defined 3D nanofiber. While proliferative capacity of human liver organoids was lost by HYDROX-culture, the gene expression level of a hepatocyte marker CYP3A4 and the CYP3A4 metabolic activity in HYDROX-cultured liver organoids were significantly improved, comparable to those of PHH. HYDROX-cultured liver organoids when treated with hepatotoxic drugs such as acetaminophen showed similar cell viability to that of PHH, suggesting that HYDROX-cultured liver organoids could be applied to drug-induced hepatotoxicity test. Furthermore, HYDROX-cultured liver organoids maintained its functions for up to 35 days and could be used to estimate chronic drug-induced hepatotoxicity such as those of fialuridine. Our findings demonstrated that human liver organoids obtained high liver functions by HYDROX-culture, meaning that HYDROX could contribute to drug discovery as a novel biomaterial.

2024-05-22 | GSE239375 | GEO

Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells

Project description:The human liver contains multiple cell types whose epigenetic patterns are undetermined. We examined the promoter methylome of purified and uncultured hepatic stellate cells (HSCs), hepatocytes (HEPs) and liver sinusoidal endothelial cells (LSECs), by methylated DNA immunoprecipitation (MeDIP) and array hybridization. Uncultured HSCs, LSECs and Heps show ~7000-8000 methylated promoters, with 60-70% similarity between all cell types. GO analysis for commonly methylated genes reveals involvement in germ cell development, segregating germ-line from somatic lineage methylation. HSCs, LSECs and HEPs also contain ~500-1000 uniquely methylated promoters; these are implicated in signaling and biosynthetic processes (HSCs), lipid transport and metabolism (LSECs), and chromatin assembly (HEPs). The promoter methylome of culture-activated HSCs deviates from that of their uncultured (quiescent) counterparts. HSC culture-induced activation also enhances methylation differences between individual donors; however this does not necessarily relate to changes in gene expression. HSc activation results in a net gain of promoter DNA methylation, despite the demethylation and de novo methylation of thousands of promoters. Our data provide to our knowledge the first genome-wide maps of promoter DNA methylation in human purified and uncultured liver cell types. Although methylation profiles are largely similar between HSCs, LSECs and hepatocytes, the detection of cell type-specific methylation patterns suggests a differential epigenetic programming of these cell types in the liver. Determine the promoter DNA methylation pattern of 3 uncultured, reshly isolated, human healthy liver cell types (hepatocytes (HEPs), liver sinusoidal endothelial cells (LSECs) and haptic stellate cells (HSCs), and of HSCs after a 24-h culture-induced activation.

2015-12-21 | E-GEOD-66796 | biostudies-arrayexpress

Gene expression data of hepatocytes derived from human fibroblasts, human iPSCs, and human adult hepatocytes

Project description:Generation of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes. Microarray analysis has been used to show: 1. post-transplant maturation in vivo of iMPC-Heps compared to aHeps, 2. differences between iMPC-Heps and freshly isolated aHeps in vitro, 3. similar profile of freshly isolated aHeps to aHeps and iMPC-Heps in vivo, and 4. similarities of expression levels of most, but not all, genes between iMPC-Heps and iPSC-Heps in vitro. We isolated repopulating nodules of iMPC-Heps and aHeps by laser-capture microscopy (LCM) around 9 months after transplantation and analyzed their gene expression on the microarray, together with RNA from in vitro samples.

2014-01-22 | E-GEOD-52309 | biostudies-arrayexpress

Gene expression data of hepatocytes derived from human fibroblasts, human iPSCs, and human adult hepatocytes

2014-01-22 | GSE52309 | GEO

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

Single cell 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 cellular composition and properties of human hepatic organoids in single cell level, we performed single cell RNA-sequencing.

2023-06-22 | GSE153019 | GEO

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