The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluritpotent cells into cells with hepatocyte characteristics. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation toward a hepatocytelike fate appeared to recapitulate many of the stages normally associated with the formation of hepatocytes in vivo. In the current study we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate i) that human ES cells express a number of mRNAs that characterize each stage in the differentiation process, ii) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses, and iii) that the nuclear hormone receptor HNF4a is essential for specification of human hepatic progenitor cells by establishing expression of the network of transcription factors that control hepatocyte cell fate.
HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells.
Specimen part, Time
View SamplesReprogrammed somatic cells offer a valuable source of pluripotent cells that have the potential to differentiate into many cells types and provide a new tool for regenerative medicine. In the present study we differentiated induced pluripotent stem cells (iPS cells) into hepatic cells. We first showed that mouse iPS cells could from a complete liver in mouse embryo (E14.5) including hepatocytes, endothelial cells, sinusoidal cells and resident macrophages. We then designed a highly efficient hepatocyte differentiation protocol using defined factors on human embryonic stem cells (ES cells). This protocol was found to generate more than 80% albumin expressing cells that show hepatic functions and express most of liver genes as shown by microarray analyses. Similar results were obtained when human iPS cells were induced to differentiate following the same procedure.
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells.
Specimen part, Cell line
View SamplesActivation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes among others. We investigated the transcriptional regulation of the AID gene, Aicda, in the class switchinducible CH12F3-2 cells, and found that the Aicda regulation involves derepression by several layers of positive regulatory elements in addition to the 5 promoter region. The 5 upstream region contains functional motifs for the response to signaling by cytokines, CD40-ligand, or stimuli that activate NF-B. The first intron contains functional binding elements for the ubiquitous silencers c-Myb and E2f and for B cellspecific activator Pax5 and E-box-binding proteins.
B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.
Specimen part
View SamplesThe differences of clinical characteristics in complex seizures induced by influenza A(H1N1)pdm09 and rotavirus gastroenteritis are well known, but the pathogenic mechanisms remain unclear. We analyzed the gene expression profiles in the peripheral whole blood cells isolated from pediatric patients using an Affymetrix oligonucleotide microarray.
Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.
Sex, Age, Specimen part, Disease, Disease stage, Subject
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Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells.
Specimen part, Cell line
View SamplesTranscriptome analysis of LSD2-depleted HepG2 cells revealed that many of the target genes were related to lipid metabolism. We found that LSD2 is an important epigenetic regulator of hepatic lipid metabolism.
Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells.
Specimen part, Cell line
View SamplesLow-intensity pulsed ultrasound (LIPUS) has been applied as a therapeutic adjunct to promote fracture healing. However, the detailed molecular mechanisms by which LIPUS promotes bone fracture healing have not yet been fully elucidated.
Genetic response to low‑intensity ultrasound on mouse ST2 bone marrow stromal cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure.
Specimen part
View SamplesTranscriptome analysis of LSD1-depleted HepG2 cells revealed that LSD1 regulates the expression of glycolytic and mitochondrial metabolism genes.
Lysine Demethylase LSD1 Coordinates Glycolytic and Mitochondrial Metabolism in Hepatocellular Carcinoma Cells.
Specimen part, Cell line
View SamplesTranscriptome analysis of LPS-stimulated bone marrow-derived dendritic cells with NR4A3 gene silencing
The Orphan Nuclear Receptor NR4A3 Is Involved in the Function of Dendritic Cells.
Specimen part
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