Transcriptome analysis of the HepG2 cells expressing hepatic transcription factors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE115423 | GEO | 2018/10/02
REPOSITORIES: GEO
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Project description:Plasticity of differentiated cells has been proved by nuclear transfer, induced pluripotent cells and transdifferentiation. Here we show that by transduction of 3 factors (FOXA3, HNF1A and HNF4A), human fetal fibroblasts can be converted to hepatocyte-like cells (hiHep cells), expressing hepatic marker genes, and acquiring many mature hepatocyte functions in vitro and in vivo. Human fetal fibroblasts (HFF) were tranfected with 3 liver enriched transcription factors (FOXA3, HNF1A, HNF4A), and converted to hepatocyte-like cells (hiHep cells). HFF and primary human hepatocytes (PHH) serve as control.
2014-03-06 | E-GEOD-42643 | biostudies-arrayexpress
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2014-03-06 | GSE42643 | GEO
Project description:To determine the downstream regulatory network of HNF4A and HNF1A, two transcription factors that play important roles in the pancreas and liver and that are associated with diabetes, we generated a comprehensive genome-wide map of the binding targets of HNF4A and HNF1A in hiPSC-derived pancreatic and hepatic cells and relevant cell lines using ChIP-Seq and molecular validation. We report binding targets of HNF4A and HNF1A that map to both known and novel gene promoters, that are common or differentially bound across different cell types and developmental stages. Overall, the detailed characterisation of the regulatory roles of HNF4A and HNF1A in pancreatic beta cells and hepatic cells will potentially shed light on how dysregulation of these factors can contribute to altered tissue development and function, and thus pathogenesis of both monogenic diabetes and T2D.
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Project description:To identify central protein kinases that potentially promote the maturation, we chemically induced liver progenitor cells (CLiPs) from mouse hepatocytes using a previously established protocol, and profiled the phosphoproteome and proteome of freshly isolated primary mouse hepatocytes (MHs) and ALBUMIN+ hepatocytes (CLiP-Hep) cells. To systematically interrogate the early regulatory events of hepatic reprogramming, we profiled the Phosphoproteome and proteome in human dermal fibroblasts (HDFs) at 2.25 days (FHH-2.25d) and 5 days (FHH-5d) after infection of lenti-virus encoding three liver-specific transcription factors, FOXA3, HNF1A and HNF4A (FHH). In this analysis, HDF infected with lenti-virus expressing GFP for 2.25 days (GFP) were used as control.
2022-08-05 | PXD035829 | iProX
Project description:Here, we chemically induced liver progenitor cells (CLiPs) from mouse hepatocytes using a previously established protocol. To identify central protein kinases (PKs) that potentially promote the maturation of lpc-Hep cells, we profiled the transcriptomes and phosphoproteomes of freshly isolated primary mouse hepatocytes (MHs) and ALBUMIN+ hepatocytes (CLiP-Heps) cells. Based on the algorithm developed by us and experiment verification, we validated three PKs that promote mouse hepatocyte maturation. Then, we use RNA sequencing technology to identify potential regulators during hepatic reprogramming with samples from HDFs 2.25 days (FHH-2.25d) and 5 days (FHH-5d) after FOXA3, HNF1A, and HNF4A (FHH) transduction, as well as HDFs transduced with GFP for 2.25 days (GFP) as the control group. After combined analysis with phosphoproteomic data with the algorithm and experiment verification, we identified 2 PKs that may be involved in hepatic reprogramming regulation. One of the five potential regulator candidates is PIM1, which can promote the progress remarkably with overexpression. Therefore, we next perform another RNA-seq to drive the molecular mechanisms under undergoing the regulation by PIM1. Finally, we revealed that cell cycle and ferroptosis pathways are involved in the regulation via PIM1.
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Project description:The transcriptional regulation of drug-metabolizing enzymes and transporters (here collectively referred to as DMEs) in the developing proximal tubule is not well understood. As in the liver, DME regulation in the PT may be mediated through nuclear receptors which are thought to “sense” deviations from homeostasis by being activated by ligands, some of which are handled by DMEs, including drug transporters. Systems analysis of transcriptomic data during kidney development predicted a set of upstream transcription factors, including Hnf4a and Hnf1a, as well as Nr3c1 (Gr), Nfe2l2 (Nrf2), Ppara, and Tp53. Motif analysis of cis-regulatory further suggested that Hnf4a and Hnf1a are the main transcriptional regulators in the PT. Available expression data from tissue-specific Hnf4a KO tissues revealed that distinct subsets of DMEs were regulated by Hnf4a in a tissue-specific manner. ChIP-seq was performed to characterize the PT-specific binding sites of Hnf4a in rat kidneys at three developmental stages (prenatal, immature, adult), which further supported a major role for Hnf4a in regulating PT gene expression, including DMEs. In ex vivo kidney organ culture, an antagonist of Hnf4a (but not a similar inactive compound) led to predicted changes in DME expression, including among others Fmo1, Cyp2d2, Cyp2d4, Nqo2, as well as organic cation transporters and organic anion transporters Slc22a1(Oct1), Slc22a2 (Oct2), Slc22a6 (Oat1), Slc22a8(Oat3), and Slc47a1(Mate1). Conversely, overexpression of Hnf1a and Hnf4a in primary mouse embryonic fibroblasts (MEFs), sometimes considered a surrogate for mesenchymal stem cells, induced expression of several of these proximal tubule DMEs, as well as epithelial markers and a PT-specific brush border marker Ggt1. These cells had organic anion transporter function. Taken together, the data strongly supports a critical role for HNF4a and Hnf1a in the tissue-specific regulation of drug handling and differentiation toward a PT cellular identity. Hnf4a binding was examined in rat kidneys at three timepoints (E20, P13 and Adult) and p300 binding was examined in adult rat kidney cortex tissue using ChIP-seq. Four corresponding input DNA samples were used as controls for peak calling.
2014-01-01 | E-GEOD-50815 | biostudies-arrayexpress
Project description:Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem/progenitor cells have only been reprogrammed for the blood and neuronal lineages. We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs). Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs). iHepSCs can be stably expanded in vitro and possess the potential of bi-directional differentiation into both hepatocytic and cholangiocytic lineages. In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells. They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury. Lineage-conversion into bi-potential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering. iHepSCs were converted form fibroblasts by transduction of Hnf1β and Foxa3. iHepSCs were induced to differentiate into hepatocyte-like cells and cholangiocytes in vitro. Totally, 9 samples including four clones of iHepSCS, one clone of LEPCs, two samples of MEFs and two samples of iHepSCs-derived cholangocytes were analyzed.
2013-07-19 | E-GEOD-48486 | biostudies-arrayexpress
Project description:To clarify the gene expression profile of iHep, microarray analysis was performed using iHeps induced by 10 TFs (Foxg1, Lcor, Hnf3b, Hnf4a, Foxo6, Cdx2, Tcf1, Foxa3 ,Tcf2, Onecut1) and 9 TFs (Onecut1 was omitted from 10 TFs). Unsupervised hierarchical clustering indicated that iHep is expressing a global transcriptional profile more similar to that of HPCs rather than that of NPCs, and suggested that TFs present in the pool acted as inducing TFs.
2011-06-07 | GSE29730 | GEO
Project description:The transcription factor hepatocyte nuclear factor four alpha (Hnf4a) has various isoforms, one of which (P1-Hnf4a) is expressed in adult liver, where it functions as a tumor suppressor by providing circadian restrains at genes promoting cell proliferation and epithelial to mesenchymal transition. High fat diet feeding promotes the loss of nuclear P1-Hnf4a activity and a gain in the pro-proliferative P2-Hnf4a isoform, which does not function as a tumor suppressor, nor provide similar circadian restraint at cell cycle-promoting genes. P2-Hnf4a is found in all Hnf4a-positive hepatocellular carcinoma. Purpose: To determine whether inducible loss of hepatic Hnf4a followed by high fat feeding predisposes a liver to hepatocellular carcinoma. Methods: Hepatic Hnf4a was inducibly knocked out in mice at six weeks of age ("H4LivKO") followed by vivarium chow ("H4LivKOVC") or high fat feeding ("H4LivKOHF")at 8 weeks of age. Control, littermate wild-type mice (WT) were also treated with tamoxifen at six weeks of age, but since they lacked the Cre transgene, Hnf4a expression remained intact. Control mice were divided into the same feeding groups as H4LivKO mice ("WTVC" and "WTHF"). Livers were harvested at 38 weeks of age and liver tissue was flash frozen in liquid nitrogen. RNA was extracted from frozen liver tissue using Trizol, and purified RNA was submitted to Novogene for quality control and RNA-seq analysis using a 250-300 bp insert cDNA library and Illumina Platform sequencing.
2019-09-07 | GSE137051 | GEO
Project description:The transcriptional regulation of drug-metabolizing enzymes and transporters (here collectively referred to as DMEs) in the developing proximal tubule is not well understood. As in the liver, DME regulation in the PT may be mediated through nuclear receptors which are thought to “sense” deviations from homeostasis by being activated by ligands, some of which are handled by DMEs, including drug transporters. Systems analysis of transcriptomic data during kidney development predicted a set of upstream transcription factors, including Hnf4a and Hnf1a, as well as Nr3c1 (Gr), Nfe2l2 (Nrf2), Ppara, and Tp53. Motif analysis of cis-regulatory further suggested that Hnf4a and Hnf1a are the main transcriptional regulators in the PT. Available expression data from tissue-specific Hnf4a KO tissues revealed that distinct subsets of DMEs were regulated by Hnf4a in a tissue-specific manner. ChIP-seq was performed to characterize the PT-specific binding sites of Hnf4a in rat kidneys at three developmental stages (prenatal, immature, adult), which further supported a major role for Hnf4a in regulating PT gene expression, including DMEs. In ex vivo kidney organ culture, an antagonist of Hnf4a (but not a similar inactive compound) led to predicted changes in DME expression, including among others Fmo1, Cyp2d2, Cyp2d4, Nqo2, as well as organic cation transporters and organic anion transporters Slc22a1(Oct1), Slc22a2 (Oct2), Slc22a6 (Oat1), Slc22a8(Oat3), and Slc47a1(Mate1). Conversely, overexpression of Hnf1a and Hnf4a in primary mouse embryonic fibroblasts (MEFs), sometimes considered a surrogate for mesenchymal stem cells, induced expression of several of these proximal tubule DMEs, as well as epithelial markers and a PT-specific brush border marker Ggt1. These cells had organic anion transporter function. Taken together, the data strongly supports a critical role for HNF4a and Hnf1a in the tissue-specific regulation of drug handling and differentiation toward a PT cellular identity.
2014-01-01 | GSE50815 | GEO