Exploring the cell signalling in hepatocyte differentiation

Vasconcellos, Rebecca; Alvarenga, Erika Costa de; Parreira, Ricardo Cambraia; Lima, Swiany Silveira; Resende, Rodrigo R.

doi:10.1016/j.cellsig.2016.08.011

Cited by 32 publications

(14 citation statements)

References 190 publications

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“…Hepatocytes are the main liver parenchymal cells, which control hepatic biochemical and metabolic functions in the liver, including triglyceride metabolism. Additional cell types within the liver include cholangiocytes, Kupffer cells, stellate cells, and endothelial cells, each of which has specialized functions in hepatic pathobiology (261). …”

Section: Introductionmentioning

confidence: 99%

Triglyceride Metabolism in the Liver

Auger

Cohen

2017

Comprehensive Physiology

623

599

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Triglyceride molecules represent the major form of storage and transport of fatty acids within cells and in the plasma. The liver is the central organ for fatty acid metabolism. Fatty acids accrue in liver by hepatocellular uptake from the plasma and by de novo biosynthesis. Fatty acids are eliminated by oxidation within the cell or by secretion into the plasma within triglyceride-rich very low-density lipoproteins. Notwithstanding high fluxes through these pathways, under normal circumstances the liver stores only small amounts of fatty acids as triglycerides. In the setting of overnutrition and obesity, hepatic fatty acid metabolism is altered, commonly leading to the accumulation of triglycerides within hepatocytes, and to a clinical condition known as nonalcoholic fatty liver disease (NAFLD). In this review, we describe the current understanding of fatty acid and triglyceride metabolism in the liver and its regulation in health and disease, identifying potential directions for future research. Advances in understanding the molecular mechanisms underlying the hepatic fat accumulation are critical to the development of targeted therapies for NAFLD. © 2018 American Physiological Society. Compr Physiol 8:1-22, 2018.

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Section: Introductionmentioning

confidence: 99%

Triglyceride Metabolism in the Liver

Auger

Cohen

2017

Comprehensive Physiology

623

599

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“…In our study, 3D culture on matrigel was adopted to reveal the differentiated potency of CK7 + SOX9 + HPCs in vitro, resulting in the aggregation and differentiation of HPCs. Since FGF9 is expressed in hepatocytes serving as a mediator of hepatocyte proliferation (Antoine et al., ) and HGF can promote proliferation and migration of HPCs and activation of liver‐specific genes (Vasconcellos, Alvarenga, Parreira, Lima, & Resende, ), we optimized the 3D differentiation culture by addition of HGF and FGF9. As a result, a better spheroids morphology and more Alb and HNF4α positive hepatocyte‐like cells were examined, presenting a higher differentiation efficiency of HPCs.…”

Section: Discussionmentioning

confidence: 99%

Clonal expansion of hepatic progenitor cells and differentiation into hepatocyte‐like cells

et al. 2019

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Hepatic progenitor cells (HPCs) in adult liver are promising for treatment of liver diseases. A biliary‐derived HPC population in adult mice has been characterized by co‐expression of stem cell marker Sry (sex determining region Y)‐box 9 (SOX9) and biliary marker cytokeratin 7 (CK7). However, isolation of these HPCs in adult healthy liver without any selection procedures remains a big challenge in this field. Here, by establishing a simple and efficient method to isolate and expand the CK7+SOX9+ HPCs in vitro as clones, we acquired a stable and largely scalable cell source. The CK7+SOX9+ progenitor cells were then further induced to differentiate into hepatocyte‐like cells with expression of mature hepatocyte markers albumin (Alb) and hepatocyte nuclear factor 4 alpha (HNF4α), both in vitro and in vivo in the presence of hepatocyte growth factor (HGF) and fibroblast growth factor 9 (FGF9). Furthermore, we found that the HPCs are highly responsive to transforming growth factor‐beta (TGF‐β) signals. Collectively, we identified and harvested a CK7+SOX9+ progenitor cell population from adult mouse liver by a simple and efficient approach. The exploration of this HPC population offers an alternative strategy of generating hepatocyte‐like cells for cell‐based therapies of acute and chronic liver disorders.

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“…However, it is limited by numerous problems, including shortage of donor organs, high cost, and immune rejection [64]. To solve these problems, stem-cell-based therapeutic strategies have emerged as alternative options [63, 65]. A recent study indicates that physiological concentrations of H 2 S could increase the ability of human tooth-pulp stem cells (HTPC) to undergo hepatogenic differentiation [66].…”

Section: H2s In Hepatic Functionmentioning

confidence: 99%

Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease

Wang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Hydrogen sulfide (H2S), a colorless gas smelling of rotten egg, has long been recognized as a toxic gas and environment pollutant. However, increasing evidence suggests that H2S acts as a novel gasotransmitter and plays important roles in a variety of physiological and pathological processes in mammals. H2S is involved in many hepatic functions, including the regulation of oxidative stress, glucose and lipid metabolism, vasculature, mitochondrial function, differentiation, and circadian rhythm. In addition, H2S contributes to the pathogenesis and treatment of a number of liver diseases, such as hepatic fibrosis, liver cirrhosis, liver cancer, hepatic ischemia/reperfusion injury, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, hepatotoxicity, and acute liver failure. In this review, the biosynthesis and metabolism of H2S in the liver are summarized and the role and mechanism of H2S in liver health and disease are further discussed.

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Exploring the cell signalling in hepatocyte differentiation

Cited by 32 publications

References 190 publications

Triglyceride Metabolism in the Liver

Triglyceride Metabolism in the Liver

Clonal expansion of hepatic progenitor cells and differentiation into hepatocyte‐like cells

Hydrogen Sulfide as a Novel Regulatory Factor in Liver Health and Disease

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