Genome-wide analysis of mRNA expression alterations in human primary hepatocytes compared with cAMP treated and non-treated human embryonic stem cell (hESC) derived hepatic populations
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE39157 | GEO | 2013/07/04
SECONDARY ACCESSION(S): PRJNA170116
REPOSITORIES: GEO
Similar Datasets
Project description:Microarrays were used to examine gene expression differences between primary human hepatocytes and hESC derived hepatoblast cultures treated or non-treated with cAMP. hESC's were differentiated with a hepatic cell lineage specific protocol that included the use of a 3-dimensional cell aggregation culturing technique. Followed by cAMP signaling, this promoted the maturation of hepatoblasts into a more hepatocyte-like population. Importantly, key enzymes related to liver function show that cAMP induced populations have a gene expression profile that is similar to primary human hepatocytes. Total RNA obtained from cultured primary hepatocytes and hESC derived hepatic populations.
2013-07-04 | E-GEOD-39157 | biostudies-arrayexpress
Project description:How the bi-potential hepatoblasts differentiate into hepatocytes and cholangiocytes remains unclear. Here, using single-cell transcriptomic analysis of hepatoblasts, hepatocytes, and cholangiocytes sorted from E10.5 to E17.5 mouse embryos, we found that hepatoblast-to-hepatocyte differentiation occurred gradually followed a linear default pathway. As more cells became fully differentiated hepatocytes, the number of proliferating cells decreased. Surprisingly, the proliferating and quiescent hepatoblasts exhibited homogeneous differentiation states at a given developmental stage. This unique feature enabled us to combine the single-cell and bulk-cell analyses to define the precise timing of the hepatoblast-to-hepatocyte transition, which occurs between E13.5 and E15.5. In contrast to hepatocyte development at almost all levels, hepatoblast-to-cholangiocyte differentiation underwent a sharp detour from the default pathway. New cholangiocyte generation occurred continuously between E11.5 and E14.5, but their maturation states at a given developmental stage were heterogeneous. Even more surprising, the number of proliferating cells increased as more progenitor cells differentiated into mature cholangiocytes. Based on an observation from the single-cell analysis, we also discovered that the protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signaling pathway promoted cholangiocyte maturation. CONCLUSIONS: Our studies have defined distinct pathways for hepatocyte and cholangiocyte development in vivo, which are critically important for understanding basic liver biology and developing effective strategies to induce stem cells to differentiate towards specific hepatic cell fates in vitro.
2017-07-14 | GSE90047 | GEO
Project description:The homeobox transcription factor Prox1 is expressed in embryonic hepatoblasts and remains expressed in adult hepatocytes. Prox1-null mice show severe deficiencies of liver development, but the underlying mechanisms are unknown. We studied the effects of Prox1 on the transcriptional profile of embryonic day-14 (ED14) met-murine-hepatocytes (ED14-MMH). These immortalized murine hepatoblasts express numerous hepatoblast markers, but not Prox1. We performed stable transfection with Prox1 cDNA, analyzed the transcriptome with Agilent mouse whole genome microarrays and validated genes by qRT-PCR. We observed more than 12-fold up-regulation of 22 genes and down-regulation of 232 genes. Numerous of these genes are involved in metabolic hepatocyte functions and may be regulated by Prox1 directly or indirectly, e.g. by down-regulation of HNF4a. Prox1 induces down-regulation of transcription factors, which are highly expressed in neighboring endodermal organs, suggesting a function during hepatoblast commitment. Prox1 does not influence proliferative activity of MMH but regulates genes involved in liver morphogenesis. We observed up-regulation of both type-IVa3 procollagen and functionally active matrix metalloproteinase-2 (MMP-2), which places Prox1 in the centre of liver matrix turnover. This is consistent with MMP-2 expression in hepatoblasts during liver development, and persistence of a basal lamina around the liver bud in Prox1-deficient mice. Our studies suggest that Prox1 is a multifunctional regulator of liver morphogenesis, hepatocyte function and commitment. Experiment Overall Design: - two samples Experiment Overall Design: - Dye Swap design with 6 arrays
2008-06-15 | E-GEOD-7867 | biostudies-arrayexpress
Project description:Transcriptional profiling of Mycobacterium tuberculosis CDC1551 comparing control butyric acid-treated cells with 20mM db-cAMP treated cells after 2hrs of treatment with shaking at 200rpm at 37C.
2014-01-23 | GSE54289 | GEO
Project description:Transcriptional profiling of Mycobacterium tuberculosis CDC1551 comparing control butyric acid-treated cells with 20mM db-cAMP treated cells after 2hrs of treatment with shaking at 200rpm at 37C. Two-condition experiment, butyric acid (Control) Vs db-cAMP treated cells (Test). Biological replicates: 3 control, 3 test. One replicate per array.
2014-01-23 | E-GEOD-54289 | biostudies-arrayexpress
Project description:The homeobox transcription factor Prox1 is expressed in embryonic hepatoblasts and remains expressed in adult hepatocytes. Prox1-null mice show severe deficiencies of liver development, but the underlying mechanisms are unknown. We studied the effects of Prox1 on the transcriptional profile of embryonic day-14 (ED14) met-murine-hepatocytes (ED14-MMH). These immortalized murine hepatoblasts express numerous hepatoblast markers, but not Prox1. We performed stable transfection with Prox1 cDNA, analyzed the transcriptome with Agilent mouse whole genome microarrays and validated genes by qRT-PCR. We observed more than 12-fold up-regulation of 22 genes and down-regulation of 232 genes. Numerous of these genes are involved in metabolic hepatocyte functions and may be regulated by Prox1 directly or indirectly, e.g. by down-regulation of HNF4a. Prox1 induces down-regulation of transcription factors, which are highly expressed in neighboring endodermal organs, suggesting a function during hepatoblast commitment. Prox1 does not influence proliferative activity of MMH but regulates genes involved in liver morphogenesis. We observed up-regulation of both type-IVa3 procollagen and functionally active matrix metalloproteinase-2 (MMP-2), which places Prox1 in the centre of liver matrix turnover. This is consistent with MMP-2 expression in hepatoblasts during liver development, and persistence of a basal lamina around the liver bud in Prox1-deficient mice. Our studies suggest that Prox1 is a multifunctional regulator of liver morphogenesis, hepatocyte function and commitment. Keywords: Met murine hepatocytes - Hex - HNF4a - MMP-2 - Type-IV collagen Keywords: Met murine hepatocytes - Hex - HNF4a - MMP-2 - Type-IV collagen
2007-05-25 | GSE7867 | GEO
Project description:Bi-potential hepatoblasts give rise to hepatocytes with the default fate choice, while undergo a regulatory fate transition to cholangiocytes. We aimed to understand how the “default” vs “regulatory” cell fate differentiations were modulated at the chromatin level. We performed chromatin immunoprecipitation sequencing (ChIP-seq) of hepatobiliary lineages to profile promoter and enhancer associated histone modifications H3K4me3, H3K27me3, H3K27ac and H3K4me1. We also performed in vivo gene manipulation and ex vivo intervention of related histone modifiers were performed to validate their roles in hepatoblast differentiation. We discovered that removal of H3K27me3 from bivalency on promoters was associated with activation of genes related to hepatoblast-cholangiocyte fate transition. In vivo gene manipulation and ex vivo intervention with H3K27me3-modifying enzymes demonstrated that Ezh2 and Jmjd3 specifically regulated hepatoblast-cholangiocyte cell fate transition. In addition, establishments of active and primed enhancers were associated with the developmental processes of both hepatocytes and cholangiocytes, and knockout of P300 inhibited these lineages development.
2023-06-26 | GSE142089 | GEO
Project description:During mouse embryogenesis, progenitors within the liver known as hepatoblasts give rise to adult hepatocytes and cholangiocytes. Hepatoblasts, which are specified at E8.5-E9.0, have been regarded as a homogeneous progenitor population that initiate differentiation from E13.5. Recently, scRNA-seq analysis has identified sub- populations of transcriptionally distinct hepatoblasts at E11.5. Here, we show that hepatoblasts are not only transcriptionally but also functionally heterogeneous, and that a subpopulation of E9.5-E10.0 hepatoblasts exhibit a previously unidentified early commitment to cholangiocyte fate. Importantly, we also identify a sub-population constituting 2% of E9.5-E10.0 hepatoblasts that express the adult stem cell marker Lgr5, and generate both hepatocyte and cholangiocyte progeny that persist for the lifespan of the mouse. Combining lineage tracing and scRNA-seq, we show that Lgr5 marks E9.5-E10.0 bipotent liver progenitors residing at the apex of a hepatoblast hierarchy. Notably, isolated Lgr5+ hepatoblasts can be clonally expanded in vitro into embryonic liver organoids, which can commit to either hepatocyte or cholangiocyte fates. Our study demonstrates functional heterogeneity within E9.5 hepatoblasts and identifies Lgr5 as a marker for a sub-population of bipotent liver progenitors.
2019-05-27 | GSE123103 | GEO
Project description:The variability in the prognosis of hepatocellular carcinoma (HCC) patients suggests that HCC may comprise several distinctive biological phenotypes. These phenotypes may result from different neoplastic pathways during the tumorigenesis and/or from a different cell of origin. Here we address if the transcriptional characteristics of the HCC would provide insight into the cellular origin of the tumors. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes, HCC from mouse models, and human HCC. The HCC patients who shared gene expression patterns with fetal hepatoblasts showed extremely poor prognosis when compared with those lacking the hepatoblast signature. The gene expression program that distinguishes this novel subtype from the rest of HCC includes well known markers of hepatic oval cells, suggesting that HCC in this subtype may arise from hepatic progenitor cells. Two independent gene network analyses of the gene expression signature characteristic for the tumors sharing the hepatoblast expression patterns revealed that activation of AP-1 transcription factors might play key roles in tumor development in the newly identified HCC subtype. In addition, by applying hepatoblast-specific and genome-wide global signatures, HCC patients were further stratified into three distinct subgroups with a significant association with overall survival and recurrence. Total RNAs from 19 normal livers were pooled and used as the reference for all microarray experiments. To obtain gene expression profile data from 49 human HCC, 20 µg of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using a dye-swap strategy to eliminate dye labeling bias.
2010-07-01 | E-GEOD-4024 | biostudies-arrayexpress
Project description:The variability in the prognosis of hepatocellular carcinoma (HCC) patients suggests that HCC may comprise several distinctive biological phenotypes. These phenotypes may result from different neoplastic pathways during the tumorigenesis and/or from a different cell of origin. Here we address if the transcriptional characteristics of the HCC would provide insight into the cellular origin of the tumors. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes, HCC from mouse models, and human HCC. The HCC patients who shared gene expression patterns with fetal hepatoblasts showed extremely poor prognosis when compared with those lacking the hepatoblast signature. The gene expression program that distinguishes this novel subtype from the rest of HCC includes well known markers of hepatic oval cells, suggesting that HCC in this subtype may arise from hepatic progenitor cells. Two independent gene network analyses of the gene expression signature characteristic for the tumors sharing the hepatoblast expression patterns revealed that activation of AP-1 transcription factors might play key roles in tumor development in the newly identified HCC subtype. In addition, by applying hepatoblast-specific and genome-wide global signatures, HCC patients were further stratified into three distinct subgroups with a significant association with overall survival and recurrence. Keywords: individual genetic characteristic design
2006-01-26 | GSE4024 | GEO