Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long-term Functional Maintenance of Primary Human Hepatocytes In Vitro

ABSTRACT: Functional maintenance of terminally differentiated cells outside the in vivo microenvironment has proved challenging. Current strategies that manipulate cell-cell or cell-matrix connections are difficult to constitute complex regulatory networks for cell function maintenance. Small molecules are easily combined for flexible spatiotemporal modulations, theoretically favorable for synergetic regulation of cell-innate signaling pathways to maintain cell function in vitro. Here, we developed small-molecule cocktails enabling robust maintenance of primary human hepatocytes (PHHs) longer than four weeks, with gene expression profiles, resembling those of freshly isolated PHHs; and prolong-cultured PHHs, for the first time, could maintain drug-metabolizing activities of enzymes accounting for over 80% of drug-oxidation and support hepatitis B virus infection in vitro for over one month. Our study demonstrates that this chemical approach effectively maintains terminally differentiated hepatocytes in vitro, which could be extended to various cell types.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108198 | GEO | 2019/04/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Global transcriptional analysis of human functional hepatocytes Long-term maintained by small-molecule cocktails by RNA-seq

Project description:Functional maintenance of terminally differentiated cells outside the in vivo microenvironment has proved challenging. Current strategies that manipulate cell-cell or cell-matrix connections are difficult to constitute complex regulatory networks for cell function maintenance. Small molecules are easily combined for flexible spatiotemporal modulations, theoretically favorable for synergetic regulation of cell-innate signaling pathways to maintain cell function in vitro. Here, we developed small-molecule cocktails enabling robust maintenance of primary human hepatocytes (PHHs) longer than four weeks, with gene expression profiles, resembling those of freshly isolated PHHs; and prolong-cultured PHHs, for the first time, could maintain drug-metabolizing activities of enzymes accounting for over 80% of drug-oxidation and support hepatitis B virus infection in vitro for over one month. Importantly, this cocktail also promotes functional maturation of human pluripotent stem cell-derived hepatocytes. Our study demonstrates that this chemical approach effectively maintains terminally differentiated hepatocytes in vitro, which could be extended to various cell types.

2019-04-26 | GSE120226 | GEO

A novel reprogramming strategy to generate functionally competent human hepatocytes

Project description:Cell fate can be directly converted between differentiated cells by lineage reprogramming, thus generating multiple cell types across developmental lineages. However, lineage reprogramming is hindered by incomplete cell-fate conversion with residual initial cell identity and partial functions compared with the native counterparts. Here, we develop a high-fidelity reprogramming strategy, by mimicking the natural cell-fate changing route, thus permitting the production of functionally competent human hepatocytes from another cell type. We first converted fibroblasts into plastic hepatic progenitor-like cells (hHPLCs) and chemically induced them into mature hepatocytes. The molecular identity of human induced hepatocytes (hiHeps) are suggested a terminally differentiated state, resembling primary human hepatocytes (PHHs). Functionally, hiHeps were competent to replace PHHs for equivalent drug-metabolizing activities, toxicity prediction and hepatitis B virus infection. Remarkably, the stably robust expansion of hHPLCs allowed large-scale generation of mature hepatocytes. Our results demonstrate the necessity of taking a reprogramming step for plastic progenitors for efficient cell-fate conversion. This strategy is promising for the generation of other mature human cell types.

2019-09-02 | GSE112330 | GEO

A novel reprogramming strategy to generate functionally competent human hepatocytes [Illumina methylation]

2021-10-26 | GSE121860 | GEO

RNA-sequencing of hepatocyte-like cells (HLCs) and primary human hepatocytes (PHHs)

Project description:The purpose of this experiment was to compared the transcriptome of hepatocyte-like cells (HLCs) generated in vitro and adult primary human hepatocytes (PHHs). HLCs were differentiated from either hESCs or hIPSCs using previously established protocols (Hannah et al 2013; Segeritz et al 2018). Undifferentiated hIPSCs were used as control to confirm differentiation status. PHHs were commercially sourced as well as freshly isolated from donors.

2022-08-11 | E-MTAB-10634 | biostudies-arrayexpress

ChIP-sequencing of hepatocyte-like cells (HLCs) and primary human hepatocytes (PHHs)

Project description:ChIP-sequencing was performed to explore the difference between the epigenetic profiles of hepatocyte-like cells (HLCs) generated in vitro and primary human hepatocytes (PHHs). HLCs were differentiated from hIPSCs and hESCs for 30 days, as previously reported (Hannan et al, 2013). PHHs were purchased from Biopredic. Chromatin was immunoprecipitated with antibodies against H3K27ac, H3K4me1, H3K27me3 and H3K4me3. Library preparation and sequencing were performed by the Wellcome Trust Sanger Institute DNA Sequencing Facility (Hinxton, UK). Sequencing was performed on an Illumina HiSeq v4 instrument to obtain paired-end reads with 75bp length.

2022-08-11 | E-MTAB-10637 | biostudies-arrayexpress

A two-step de-differentiation and maturation of primary human hepatocytes in vitro with efficient metabolic and regenerative capacities

Project description:Hepatocytes hold significant promise for applications in drug screening, disease modeling, and clinical cell transplantation. Generating large amouts of hepatocyte in vitro for those application is still challenging. We have previously established a 5C medium for long-term culture and functional maintanace human primary hepatocytes (PHHs) in vitro. However, 5C condtion could not support hepatocyte expansion, which limited its application. In this study, we established a new hepatocyte expansion medium (NHEM) for efficient hepatocyte expansion, which turned the PHHs into hepatic progenitor-like cells (HPLCs). We also generated an optimized 6C condtion for HPLCs maturation. Overall, this study provide a new strategy to generate large amounts of hepatocytes in vitro.

2024-09-23 | GSE261965 | GEO

A two-step de-differentiation and maturation of primary human hepatocytes in vitro with efficient metabolic and regenerative capacities

2024-09-23 | GSE261962 | GEO

Limited oxygen availability in standard cell culture alters metabolism and function in terminally differentiated cells

Project description:<p>Cell culture is generally considered to be hyperoxic. However, the importance of cellular oxygen consumption is often underappreciated, with rates of oxygen consumption often sufficient to cause hypoxia at cell monolayers. We initially focused on cultured adipocytes as a terminally differentiated cell-type with substantial oxygen consumption rates to support diverse cellular functions. Under standard conditions, cultured adipocytes are hypoxic and highly glycolytic. Increasing oxygen diverted glucose flux toward mitochondria and resulted in thousands of gene expression changes that pointed toward alleviated physiological transcriptional responses to hypoxia. Phenotypically, providing more oxygen increased adipokine secretion and rendered adipocytes more sensitive to insulin and lipolytic stimuli. The functional benefits of increasing pericellular oxygen were transferable to other cellular systems including hPSC-derived hepatocytes and cardiac organoids. Our findings suggest that oxygen is limiting in many terminally-differentiated cell culture systems, and that controlling oxygen availability can improve the quality and translatability of cell models.</p>

2024-02-21 | MTBLS6677 | MetaboLights

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

Transmitted/founder hepatitis C viruses induce cell type- and genotype-specific differences in innate signaling within the liver

Project description:Primary human hepatocytes (PHHs) are a liver-specific cell subtype, and we have shown that these cells respond in a unique manner to the introduction of hepatitis C viral RNA (HCV vRNA) derived from different genotypes of the virus. We used microarray to analyze the transcriptional differences between the PHHs exposed to the different genotypes of HCV to further shed light on their differential effects on HCV innate immune responses in vitro HCV vRNA from either genotype 3a HCV or genotype 1a HCV was introduced into the PHH cells for 8 hours. Total RNA was then harvested to determine transcriptional differences.

2014-12-20 | E-GEOD-64400 | biostudies-arrayexpress

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