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Hepatocytes obtained from mouse GPSCs are functional and show similar expression profiles to fetal primary hepatocytes

ABSTRACT: Germline cell-derived pluripotent stem cells (GPSCs) are similar to embryonic stem (ES) cells in that they can proliferate intensively and differentiate into a variety of cell types, including cardiomyocytes and neurons. In this report, mouse GPSCs were induced to differentiate into hepatocytes with very high efficiency, and demonstrated, for the first time, to be functional. These hepatocytes were characterised at cellular and molecular levels. The GPSC-derived hepatocytes not only expressed hepatic markers, but were also metabolically active as shown by albumin and haptoglobin secretion, urea synthesis, glycogen storage and indocyanine green uptake. Previous studies have revealed some inherent differences in gene expression between undifferentiated mouse ES cells and GPSCs. We wanted to investigate whether this difference may impact on the hepatocyte differentiation capacity of the GPSCs. Large-scale gene expression profiling revealed a strong similarity between GPSC and ES cells at different stages of induced hepatic differentiation. Moreover, Pearson correlation analysis of the microarray datasets revealed that, at late hepatic differentiation stages, the in vitro-derived cells were closer to fetal mouse primary hepatocytes. Thus, adult GPSCs offer great potential for cell ment therapy for a wide variety of liver diseases. Mouse ES cells and GPSCs at various times of hepatocyte differentiation, compared to embryonal (E16) and postnatal (PN1) mouse primary hepatocytes. The supplementary file 'GSE19044_non-normalized.txt' contains non-normalized data for Samples GSM471318-GSM471359.

ORGANISM(S): Mus musculus

SUBMITTER: Sharmila Fagoonee

PROVIDER: E-GEOD-19044 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Hepatocytes obtained from mouse GPSCs are functional and show similar expression profiles to fetal primary hepatocytes

Project description:Germline cell-derived pluripotent stem cells (GPSCs) are similar to embryonic stem (ES) cells in that they can proliferate intensively and differentiate into a variety of cell types, including cardiomyocytes and neurons. In this report, mouse GPSCs were induced to differentiate into hepatocytes with very high efficiency, and demonstrated, for the first time, to be functional. These hepatocytes were characterised at cellular and molecular levels. The GPSC-derived hepatocytes not only expressed hepatic markers, but were also metabolically active as shown by albumin and haptoglobin secretion, urea synthesis, glycogen storage and indocyanine green uptake. Previous studies have revealed some inherent differences in gene expression between undifferentiated mouse ES cells and GPSCs. We wanted to investigate whether this difference may impact on the hepatocyte differentiation capacity of the GPSCs. Large-scale gene expression profiling revealed a strong similarity between GPSC and ES cells at different stages of induced hepatic differentiation. Moreover, Pearson correlation analysis of the microarray datasets revealed that, at late hepatic differentiation stages, the in vitro-derived cells were closer to fetal mouse primary hepatocytes. Thus, adult GPSCs offer great potential for cell ment therapy for a wide variety of liver diseases.

2010-06-01 | GSE19044 | GEO

Gp130-dependent release of acute phase proteins is linked to the activation of innate immune signaling pathways

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2010-11-13 | E-GEOD-25278 | biostudies-arrayexpress

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Project description:Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). MYDGF also enhances proliferation of human hepatocytes in three-dimensional organoids. In vivo, genetic deletion of MYDGF decreases hepatocyte proliferation in the regenerating mouse liver after PHx; conversely, adeno-associated viral delivery of MYDGF increases hepatocyte proliferation and MAPK signaling after PHx. We conclude that MYDGF represents a mechanically-induced angiocrine signal and that it triggers growth of, and provides protection to, primary mouse and human hepatocytes

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2022-11-19 | GSE215423 | GEO

Gene expression profiles in human liver organoid-derived hepatocytes

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2021-07-26 | GSE176069 | GEO

Conversion of terminally committed mouse hepatocytes to culturable bipotent progenitor cells

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CDK5RAP3 regulates hepatocyte differentiation in human

Project description:CDK5RAP3, an UFL1 adaptor for UFMylation, is crucial for liver development in mouse. However, the function of CDK5RAP3 in human hepatocyte differentiation remains unclear. The stepwise generation of hepatocyte-like cells derived from human embryonic cells simulates human hepatocyte differentiation in vitro. Here, the human embryonic cells were conducted to differentiate into hepatocytes and ScRNA-Seq analysis was performed to elucidate the molecular mechanism of CDK5RAP3 in human liver development. We found CDK5RAP3 was important for human hepatocytes differentiation. The CDK5RAP3 deficiency upregulated ER stress in hepatic-endoderm stage, and impaired ribosome homeostasis in mature hepatocytes.

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