Expression data from hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE187011 | GEO | 2021/11/03
REPOSITORIES: GEO
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Project description:We investigated the transcriptome of human induced pluripotent stem cells (hiPSCs) differentiated into hepatocyte-like cells (HLCs) in a biochip culture environment vs. standard Petri dishes cultures using nanoCAGE, a method for promoters, transcription factors, and transcriptome analysis.
2020-12-01 | GSE149806 | GEO
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
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
Project description:Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPSHLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drugmetabolizing capacity and drug responsiveness.
2014-11-12 | GSE61287 | GEO
Project description:We investigated the human induced pluripotent stem cells (hiPSCs) during a sequential in vitro step-by-step differentiation into hepatocyte-like cells (HLCs) using nanoCAGE, a method for promoters, transcription factors, and transcriptome analysis.
2019-09-05 | GSE136841 | GEO
Project description:Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver disease and to test drugs. However, despite their advantages over other hepatocyte culture systems, HLCs lack several in vivo characteristics including cell polarity, which is critical for proper hepatocyte biology. We report a stem cell-based differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined basolateral and apical membranes separated by tight junctions. Unlike conventional HLCs, polarized HLCs secrete cargo directionally, similar to hepatocytes in vivo. This novel system provides a powerful tool to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism in a more physiologically relevant setting.
2020-02-25 | GSE123462 | GEO
Project description:Hepatocyte-like cells (HLCs) are derived from human pluripotent stem cells (hPSCs) in vitro, but differentiation protocols commonly give rise to a heterogeneous mixture of cells. This variability confounds the evaluation of in vitro functional assays performed using HLCs. We demonstrate the purification of a sub-population of functional HLCs differentiated from multiple hPSC lines using the hepatocyte surface marker Asialoglycoprotein Receptor 1 (ASGR1). We analyzed the expression profile of ASGR1-positive cells by microarray, and tested their ability to perform mature hepatocyte functions (albumin and urea secretion, cytochrome activity). By these measures, ASGR1-positive HLCs are enriched for the gene expression profile and functional characteristics of primary hepatocytes compared to unsorted HLCs.
2016-01-22 | GSE77086 | GEO
Project description:Background Metabolic dysfunction-associated steatotic liver disease (MAFLD) has a high prevalence and high co-morbidity for other diseases. Due to the complexity of this multifactorial disease, therapy options are still rather limited. We employed an in vitro pluripotent stem cell-based model to decipher potential disease-associated molecular pathways and to study the mode of action of prospective drugs. Dipeptidyl peptidase 4 (DPP4) or Cluster of differentiation 26 (CD26) is involved in inflammation, infections, immune disorders, type 2 diabetes, kidney disease and cancer. Methods We induced the steatosis phenotype in human induced pluripotent stem cell (iPSC) derived hepatocyte-like cells (HLCs) by oleic acid (OA)-feeding and confirmed regulation of clinically relevant pathways by NGS-based global transcriptomic analyses. Analysis of the secretome of steatotic HLCs revealed DPP4 as a potential key mediator of the disease. To further elucidate its role in the development of MAFLD, we inhibited DPP4 activity with Vildagliptin (VILDA) and analyzed the global transcriptome changes as well as specific gene and protein expression of steatosis-associated genes with and without DPP4 inhibition. Results MAFLD-associated pathways such as PPAR- and TNF signaling were differentially regulated in hiPSC-derived steatotic HLCs. We found increased hepatic DPP4 activity and secretion upon OA. Gene expression of fatty acid and purine metabolism and inflammation-associated pathways were regulated upon DPP4 inhibition. Conclusions Our HLC-model confirmed association of DPP4 with metabolism and inflammation which foster the development of MAFLD. Inhibiting DPP4 with VILDA partially relieved the steatotic phenotype on a global transcriptomic level. Impact and implications Given the difficulties of identifying suitable anti-MAFLD drugs, novel model systems are urgently needed. Our in vitro HLC-model reproduced DPP4-dependent aspects of the disease and responded positively to Vildagliptin treatment. Further elucidation of the role of DPP4 in the etiology of MAFLD and other diseases is warranted.
2026-03-18 | GSE310214 | GEO
Project description:Background Metabolic dysfunction-associated steatotic liver disease (MAFLD) has a high prevalence and high co-morbidity for other diseases. Due to the complexity of this multifactorial disease, therapy options are still rather limited. We employed an in vitro pluripotent stem cell-based model to decipher potential disease-associated molecular pathways and to study the mode of action of prospective drugs. Dipeptidyl peptidase 4 (DPP4) or Cluster of differentiation 26 (CD26) is involved in inflammation, infections, immune disorders, type 2 diabetes, kidney disease and cancer. Methods We induced the steatosis phenotype in human induced pluripotent stem cell (iPSC) derived hepatocyte-like cells (HLCs) by oleic acid (OA)-feeding and confirmed regulation of clinically relevant pathways by NGS-based global transcriptomic analyses. Analysis of the secretome of steatotic HLCs revealed DPP4 as a potential key mediator of the disease. To further elucidate its role in the development of MAFLD, we inhibited DPP4 activity with Vildagliptin (VILDA) and analyzed the global transcriptome changes as well as specific gene and protein expression of steatosis-associated genes with and without DPP4 inhibition. Results MAFLD-associated pathways such as PPAR- and TNF signaling were differentially regulated in hiPSC-derived steatotic HLCs. We found increased hepatic DPP4 activity and secretion upon OA. Gene expression of fatty acid and purine metabolism and inflammation-associated pathways were regulated upon DPP4 inhibition. Conclusions Our HLC-model confirmed association of DPP4 with metabolism and inflammation which foster the development of MAFLD. Inhibiting DPP4 with VILDA partially relieved the steatotic phenotype on a global transcriptomic level. Impact and implications Given the difficulties of identifying suitable anti-MAFLD drugs, novel model systems are urgently needed. Our in vitro HLC-model reproduced DPP4-dependent aspects of the disease and responded positively to Vildagliptin treatment. Further elucidation of the role of DPP4 in the etiology of MAFLD and other diseases is warranted.
2026-03-18 | GSE310216 | GEO
Project description:Hepatocyte-like cells derived from human pluripotent stem cells (hPSC-HLCs) offer an alternative to primary hepatocytes commonly used for drug screenings and toxicological tests. However, these cells do not have hepatic functions comparable to those of hepatocytes in vivo due to insufficient hepatic differentiation. Here we showed that the hepatic functions of hPSC-HLCs were facilitated by applying physiological liver temperatures during hepatic differentiation. We identified the optimal temperature by treating HLCs derived from H9 human embryonic stem cells (hESC-HLCs) at 39 °C; the 42 °C treatment caused significantly greater cell death than the 39 °C treatment. We confirmed the improvement of hepatic functions, such as albumin secretion, cytochrome P450 3A activity, and collagen production, without severe cell damage. In combination with existing hepatic differentiation protocols, the method proposed here may further improve hepatic functions for hPSCs and lead to the realization of drug discovery efforts and drug toxicological tests.
2022-03-29 | GSE172227 | GEO