Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA170116 | ENA |
REPOSITORIES: ENA
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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: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
2015-07-08 | E-GEOD-39157 | ExpressionAtlas
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.
2013-07-04 | GSE39157 | GEO
Project description:The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.
2021-04-20 | GSE128060 | GEO
Project description:Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions. In contrast, negative Cx32 regulator 2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted hepatocyte functions through disruption of GJIC activities. Dynamic gap junction organization and internalization are phosphorylation-dependent and the p38 mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK inhibitor SB203580 improved maturation of hESC-Heps correlating with up-regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC-Heps maturation correlating with down-regulation of Cx32. These results suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation.
2017-02-12 | GSE76098 | 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
Project description:Rodent lipid metabolism and postnatal nutrition is fundamentally different from humans. Therefore, we used embryonic stem cells (hESC) to model hepatic development in human. Pluripotent stem cells reliably produce hepatocytes with neonatal characteristics5. Postpartum was mimicked by the removal of oncostatin M (OSM), lost due to the migration of hematopoietic cells to the bone marrow after birth, and the concomitant addition of oleic acid (OA) and linoleic acid (LA), major components of breast milk.
2019-08-13 | GSE135713 | GEO
Project description:Transcriptomic analysis of undifferentiated hESC, hESC -derived cell populations and human Embryonic Liver (EL) cell populations.
| PRJNA800383 | ENA
Project description:Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long term survival of engrafting cells in the body, not only do the cells have to execute liverspecific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 postdifferentiation), hepatoblast (day 15) and immature hepatocytes (day 21) from human embryonic stem cells (hESC). Day 5, 15 and 21 cells were stimulated with IFN-α and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-α treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFNstimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatocytes upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs – LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival.
2016-09-22 | GSE67848 | GEO
Project description:Stem cell derived somatic cells represent an unlimited resource for basic and translational science. While promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes, which is the product of using undefined components in the differentiation process. To tackle this issue, we have designed a defined differentiation process using recombinant laminin substrates as extracellular matrix support, and compared the hepatic differentiation potential obtained with this matrix to that of matrigel. Human embryonic stem cells H9 were replated onto matrigel, pure laminin 521 and the laminin 521:111 mix (1:3 ratio, referred to as laminin 111 mix) coated wells.
2016-01-18 | E-MTAB-3994 | biostudies-arrayexpress