Transcription Factors in Liver Development, Differentiation, and Regeneration

Costa, Robert H.; Kalinichenko, Vladimir V.; Holterman, Ai Xuan; Wang, Xinhe

doi:10.1016/j.hep.2003.09.034

Cited by 355 publications

(210 citation statements)

References 195 publications

(258 reference statements)

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“…Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes, including certain genes that are important for hepatic functions, such as morphological and functional differentiation of hepatocytes, glucose transport and metabolism [83]. Among the HNFs, HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1 have been shown to play essential roles in hepatic/pancreatic/intestine development [84].…”

Section: Resultsmentioning

confidence: 99%

Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver

He²,

Huang³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver. Methods and Results: Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk) and hepatocyte markers (AFP, Alb and ApoB). Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks. Conclusions: We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation.

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Section: Resultsmentioning

confidence: 99%

Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver

He²,

Huang³

et al. 2014

Cell Physiol Biochem

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“…C/EBPa levels are significantly reduced, while those of C/EBPb are upregulated early after the intervention [143,146]. These changes appear to be important for normal hepatic regeneration, as C/Ebpb null mice have defective glucose homeostasis and display impaired liver regeneration [147,148], and C/EBPa may restrain hepatocellular proliferative activity [3]. Nevertheless, cooperative interactions between liver-enriched transcription factors need to occur during regeneration to allow cell proliferation while maintaining liver function.…”

Section: Regulation Of Hepatocellular Quiescence and Proliferationmentioning

confidence: 99%

“…To carry out their complex and varied functions, for which the preservation of their tridimensional organization within the lobule is essential, hepatocytes must express a large complement of enabling genes [3]. Understanding how the pattern of gene expression that defines hepatocellular identity is established has been the subject of intense study for more than two decades, and the principles guiding early hepatic development and differentiation are relatively well known [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Regulation of hepatocyte identity and quiescence

Berasain

Avila

2015

Cell. Mol. Life Sci.

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The liver is a highly differentiated organ with a central role in metabolism, detoxification and systemic homeostasis. To perform its multiple tasks, liver parenchymal cells, the hepatocytes, express a large complement of enabling genes defining their complex phenotype. This phenotype is progressively acquired during fetal development and needs to be maintained in adulthood to guarantee the individual's survival. Upon injury or loss of functional mass, the liver displays an extraordinary regenerative response, mainly based on the proliferation of hepatocytes which otherwise are long-lived quiescent cells. Increasing observations suggest that loss of hepatocellular differentiation and quiescence underlie liver malfunction in chronic liver disease and pave the way for hepatocellular carcinoma development. Here, we briefly review the essential mechanisms leading to the acquisition of liver maturity. We also identify the key molecular factors involved in the preservation of hepatocellular homeostasis and finally discuss potential strategies to preserve liver identity and function.

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“…Here we reported for the first time that hepatic expression of HNF4α was significantly abundant in fast growing broiler chicken embryos livers than that of slow growing breed. This could be due to the fact that HNF4α play a critical role in liver morphogenesis (Chen et al, 1994;Zaret, 2000;Zaret, 2002) differentiation (Costa et al, 2003) and metabolism (Gonzalez, 2008). Previous studies reported that dexamethasone (Synthetic GCs) mediated up-regulation of human CYP2A6 involves the glucocorticoid receptor and increased binding of HNF4α to the Proximal Promoter (Onica et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte Nuclear Factor 4-α, Glucocorticoid Receptor and Heat Shock Protein 70 mRNA Expression during Embryonic Development in Chickens

Ahmed¹,

Musa²,

Musa³

2015

J. Anim. Health Prod.

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| Glucocorticoids (GCs) play a vital role during embryonic development. Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor that has been shown to be crucial for hepatocyte differentiation and development of the liver. Here we aimed to disclose the differences in embryonic expression of hepatic HNF4-α, glucocorticoid receptor (GR) and heat shock protein 70 (HSP70) between slow and fast growing broiler chickens embryos. Fast-growing chicken and slow-growing chicken eggs were incubated and liver samples from the embryonic development at embryo 10 (E10), (E14), (E18) and day 1 post hatch (D1) were collected. Quantitative PCR used to measure hepatic mRNA expression of GR, HSP70 and HNF4-α. Hepatic mRNA expression of HNF4-α was significantly higher in fast-growing chicken embryos at all the embryonic stages investigated. However, hepatic GR mRNA expression was significantly higher in fast-growing chicken embryos only on E10. Hepatic mRNA expression of HSP70 was significantly (P<0.05) higher in fast-growing chicken embryos at E18 and D1 posthatch stages. Our data may provide the first evidence that hepatic expression of HNF4-α, GR and HSP70 differs between fast-growing and slow-growing chickens embryos, which may account to some extent for the breed disparities in embryonic development. Fedail JF (2015). Hepatocyte nuclear factor 4-α, glucocorticoid receptor and heat shock protein 70 mRNA expression during embryonic development in chickens. Keywords

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Transcription Factors in Liver Development, Differentiation, and Regeneration

Cited by 355 publications

References 195 publications

Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver

Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver

Regulation of hepatocyte identity and quiescence

Hepatocyte Nuclear Factor 4-α, Glucocorticoid Receptor and Heat Shock Protein 70 mRNA Expression during Embryonic Development in Chickens

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