Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long-Term Cell Fate and Functional Maintenance of Human Hepatocyte through Stepwise Culture Configuration

ABSTRACT: Long-Term Cell Fate and Functional Maintenance of Human Hepatocyte through Stepwise Culture Configuration

PROVIDER: PRJNA857671 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR20077430_1.fastq.gz	Fastqsanger.gz
	SRR20077430_2.fastq.gz	Fastqsanger.gz
	SRR20077431_1.fastq.gz	Fastqsanger.gz
	SRR20077431_2.fastq.gz	Fastqsanger.gz
	SRR20077432_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 20

Similar Datasets

Long-term cell fate and functional maintenance of human hepatocyte through stepwise culture configuration.

Project description:Human hepatocyte culture system represents by far the most physiologically relevant model for our understanding of liver biology and diseases; however, its versatility has been limited due to the rapid and progressive loss of genuine characteristics, indicating the inadequacy of in vitro milieu for fate maintenance. This study, therefore, is designed to define environmental requirements necessary to sustain the homeostasis of terminally differentiated hepatocytes. Our study reveals that the supplementation of dimethyl sulfoxide (DMSO) is indispensable in mitigating fate deterioration and promoting adaptation to the in vitro environment, resulting in the restoration of tight cell-cell contact, cellular architecture, and polarity. The morphological recovery was overall accompanied by the restoration of hepatocyte marker gene expression, highlighting the interdependence between the cellular architecture and the maintenance of cell fate. However, beyond the recovery phase culture, DMSO supplementation is deemed detrimental due to the potent inhibitory effect on a multitude of hepatocyte functionalities while its withdrawal results in the loss of cell fate. In search of DMSO substitute, our screening of organic substances led to the identification of dimethyl sulfone (DMSO2), which supports the long-term maintenance of proper morphology, marker gene expression, and hepatocytic functions. Moreover, hepatocytes maintained DMSO2 exhibited clinically relevant toxicity in response to prolonged exposure to xenobiotics as well as alcohol. These observations suggest that the stepwise culture configuration consisting of the consecutive supplementation of DMSO and DMSO2 confers the microenvironment essential for the fate and functional maintenance of terminally differentiated human hepatocytes.

| S-EPMC9830592 | biostudies-literature

Long-Term Cell Fate and Functional Maintenance of Human Hepatocyte through Stepwise Culture Configuration

Project description:Humanized Liver Chimeric Mice (HLCM)-derived human hepatocytes (HLCM-HH) were maintained in the absence (non-treatment; NT) or presence of either 2% DMSO or DMSO2 (140mM)-containing medium for 7 days. HepG2 cells and Huh7 cells were cultured with 2% DMSO containing medium for 7 days. Then total cellular RNA was extracted for the subsequent poly-A based mRNA sequencing analysis.

2023-01-12 | GSE207912 | GEO

CDK5RAP3 regulates hepatocyte differentiation in human

Project description:CDK5RAP3, an UFL1 adaptor for UFMylation, is crucial for liver development in mouse. However, the function of CDK5RAP3 in human hepatocyte differentiation remains unclear. The stepwise generation of hepatocyte-like cells derived from human embryonic cells simulates human hepatocyte differentiation in vitro. Here, the human embryonic cells were conducted to differentiate into hepatocytes and ScRNA-Seq analysis was performed to elucidate the molecular mechanism of CDK5RAP3 in human liver development. We found CDK5RAP3 was important for human hepatocytes differentiation. The CDK5RAP3 deficiency upregulated ER stress in hepatic-endoderm stage, and impaired ribosome homeostasis in mature hepatocytes.

2024-01-13 | GSE253134 | GEO

Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis

Project description:Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. Regulating cell identity requires gene activation and repression. While master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether unwanted plasticity is actively suppressed by lineage-specific repressors. Here, we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that Prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternate fate master regulators. In line with patient data, PROX1 overexpression in mice blocked initiation and progression of hepatocellular carcinoma and extended survival. Remarkably, Prox1 depletion caused hepatocyte fate loss in vitro, and promoted transdifferentiation of hepatocellular- to cholangio-carcinoma in vivo. Our findings provide mechanistic evidence for PROX1 as a hepatocyte-specific safeguard and support a model where individual cell type-specific repressors actively suppress plasticity throughout life to safeguard lineage choice and prevent disease.

2024-11-11 | PXD053043 | Pride

Microbiota configuration dictates nutritional immune optimization

Project description:Microbiota configuration dictates nutritional immune optimization

| PRJNA928085 | ENA

The extent of liver injury determines hepatocyte fate toward senescence or cancer

Project description:Induction of hepatocyte senescence is known to inhibit hepatocellular carcinoma (HCC). Until now, it has not been clear how the degree of liver injury dictates hepatocyte senescence and carcinogenesis. In this study, we investigated whether the severity of injury determines cell fate decisions between hepatocyte senescence and carcinogenesis. After testing of different degrees of liver injury, we found that hepatocyte senescence is strongly induced in the setting of severe acute liver injury. Longer-term, moderate liver injury did not result into hepatocyte senescence, but instead led to a significant incidence of HCC. In addition, carcinogenesis was significantly reduced by the induction of severe acute injury after chronic moderate liver injury. We conclude that severe acute liver injury leads to hepatocyte senescence along with a low incidence of HCC, whereas chronic moderate injury allows hepatocytes to proliferate rather than to enter into senescence, and correlates with a high incidence of HCC. This study improves our understanding in hepatocyte cell fate decisions and suggests a potential clinical strategy to induce senescence to treat HCC.

2018-12-20 | GSE108328 | GEO

Maintenance of primary hepatocyte functions in vitro by inhibiting mechanical tension-induced YAP activation

Project description:Maintenance of primary hepatocyte functions in vitro by inhibiting mechanical tension-induced YAP activation

| PRJNA574958 | ENA

Hepatocyte maturation

Project description:Hepatocyte maturation

| PRJNA369428 | ENA

Multiple Niche Compartments Orchestrate Stepwise Stem Cell Lineage Differentiation

Project description:The niche controls stem cell self-renewal and progenitor differentiation for maintaining adult tissue homeostasis in various organisms. However, it remains unclear if the niche is compartmentalized to control stem cell self-renewal and stepwise progeny differentiation. In the Drosophila ovary, inner germarial sheath (IGS) cells form a niche for controlling germline stem cell (GSC) progeny differentiation. In this study, we have identified four IGS subpopulations, which form linearly arranged niche compartments for controlling GSC maintenance and multi-step progeny differentiation. Single-cell analysis of the adult ovary has identified four IGS subpopulations (IGS1-4), which identities and cellular locations have been further confirmed by fluorescent in situ hybridization. IGS1 and IGS2 physically interact with GSCs and mitotic cysts to control GSC maintenance and cyst formation, respectively, whereas IGS3 and IGS4 physically interact with 16-cell cysts to regulate meiosis and oocyte development. Finally, one follicle cell progenitor population has also been transcriptionally defined for facilitating future studies on follicle stem cell regulation. Therefore, this study has structurally revealed that the niche is organized into multiple compartments for orchestrating stepwise adult stem cell development, and has also provided useful resources and tools for further functional characterization of the niche in the future.

2020-12-23 | GSE143817 | GEO

Maintenance of primary hepatocyte functions in vitro by inhibiting mechanical tension-induced YAP activation

Project description:It has been a long-standing challenge to maintain the functions of hepatocytes in vitro. In the present study, we found that mechanical tension-induced yes-associated protein (Yap) activation triggered hepatocyte dedifferentiation. Alleviation of mechanical tension by confinement of cell spreading was sufficient to inhibit hepatocyte dedifferentiation. Based on this finding, we identified a small molecular cocktail LBDXL through reiterative chemical screening that could maintain hepatocyte functions over the long term and in vivo repopulation capacity by targeting actin polymerization and actomyosin contraction.

2019-10-30 | GSE138158 | 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