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Liver regeneration patterns in hiPSCs-derived HLCs matured on-chip

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149806 | GEO | 2020/12/01

REPOSITORIES: GEO

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Influence of CPM-dependent sorting on the multi-omics profile of hepatocyte-like cells matured in microscale biochips.

Project description:We investigated the transcriptome of human induced pluripotent stem cells (hiPSCs) differentiated into hepatocyte-like cells (HLCs) in a biochip culture environment with or without carboxypeptidase M positive (CPM+) cells selection using nanoCAGE, a method for promoters, transcription factors, and transcriptome analysis.

2021-12-01 | GSE179713 | GEO

Transcriptome profiling of derived-hepatocyte progenitors from human iPSCs with nanoCAGE

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

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

Liver regeneration patterns in hiPSCs-derived HLCs matured on-chip

Project description:Liver regeneration patterns in hiPSCs-derived HLCs matured on-chip

| PRJNA630204 | ENA

Comparative analysis of hESCs and iPSCs-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation

Project description:Two independent protocols for deriving HLCs from hESCs and iPSCs were adopted and further characterization included immunocytochemistry, real-time RT-PCR, and in vitro functional assays. Comparative microarray-based gene expression profiling was conducted on these cells and compared to the transcriptomes of human fetal liver and adult liver progenitors. HLCs derived from hESCs and hiPSCs showed significant functional similarities, similar expression of genes important for liver physiology and common pathways. However, specific differences between the two cell types could be observed. Total RNA obtained from undifferentiated hESCs, iPSCs, HLCs (hepatocyte-like cells)-derived from hESCs and iPSCs, fetal forskin fibroblasts and fetal liver.

2011-01-20 | E-GEOD-25744 | 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

Transcriptional profiling of stem cell-derived polarized hepatocytes

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

Systematic comparison of cellular adaptive stress response activation networks in hepatic stem cell-derived progeny and primary human hepatocytes

Project description:Various adaptive cellular stress response pathways are critical in the pathophysiology of liver disease and drug-induced liver injury. Human-induced pluripotent stem cell (hiPSC)-derived hepatocyte-like cells (HLCs) provide a promising tool to study cellular stress response pathways, but in this context there is limited insight on how HLCs compare to primary human hepatocytes (PHH). Here, we systematically compared the activation of four different stress pathways in PHH, HepG2 liver cancer cells, hiPSCs and different stages within the differentiation towards HLCs (definitive endoderm, hepatoblast, immature hepatocytes and HLCs). We exposed all different cell types in a concentration response to four different compounds that specifically activate the oxidative stress response (diethyl-maleate), unfolded protein response (tunicamycin), DNA damage response (cisplatin) and inflammatory signalling (TNF). We used targeted RNA-sequencing to map concentration response transcriptional similarities and differences using bench-mark concentration modelling for the various stress responses in the different test systems. We observed that HLCs are more sensitive to oxidative stress than PHH showing activation at ten-fold lower concentrations and induce a strong anti-oxidant response. Although similar UPR gene sets were activated in HLCs compared to PHH, PHH were about ten times more sensitive. Furthermore, HLCs were highly sensitive to inflammation conditions similar to HepG2 cells and in sharp contrast to hiPSC, which showed hardly any response. On the contrary, hiPSC and HepG2 were highly sensitive to DNA damage signalling while HLCs resisted a strong p53 DNA damage response upon exposure. Overall, the data indicate that despite limitation in full hepatocyte maturation, HLCs did gain specific adaptive cellular stress response networks that mimic those of PHHs.

2021-02-18 | GSE155771 | GEO

Hepatocyte-like cells

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

RNA-sequencing of forward programmed hepatocytes and fetal liver samples

Project description:The purpose of this experiment was to compare the transcriptome of FoP-Heps, with undifferentiated hiPSCs, HLCs generated by direct differentiation, and primary samples (adult and fetal). FoP-Heps where generated in vitro from hESCs by forward programming (FoP) using a combination of 4 transcription factors (HNF1A, FOXA3, HNF6, RORc). Human fetal liver samples where obtained from first trimester embryos.

2022-08-11 | E-MTAB-11852 | biostudies-arrayexpress

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