Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration

Sahoo, Sarthak; Mishra, Ashutosh; Diehl, Anna Mae; Jolly, Mohit Kumar

doi:10.1016/j.isci.2022.104955

Cited by 11 publications

(6 citation statements)

References 76 publications

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“…In the liver, cholangiocytes and hepatocytes are the two main types of epithelial cells derived from hepatoblasts (embryonic liver stem cells) and are found in the liver parenchyma ( Dianat et al, 2014 ; Huang et al, 2022 ; Sahoo et al, 2022 ). Cholangiocytes are biliary epithelial cells that line the bile ducts ( Wang et al, 2022 ).…”

Section: Parenchymal Cells: Cholangiocytesmentioning

confidence: 99%

“…They make up only 3%–5% of the total liver mass but play an important role in the production and homeostasis of bile, a digestive fluid that contributes to cholesterol excretion and detoxification in the liver ( Boyer, 2013 ; Wang et al, 2022 ). Cholangiocytes also have liver regenerative potential ( Sahoo et al, 2022 ). After liver injury, self-replication of hepatocytes is essential for maintaining liver size and function ( Huang et al, 2022 ).…”

Section: Parenchymal Cells: Cholangiocytesmentioning

confidence: 99%

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Cellular heterogeneity and plasticity during NAFLD progression

Park

Choi

Kim

et al. 2023

Front. Mol. Biosci.

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Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that can progress to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis, and hepatocellular carcinoma (HCC). NAFLD ranges from simple steatosis (or nonalcoholic fatty liver [NAFL]) to NASH as a progressive form of NAFL, which is characterized by steatosis, lobular inflammation, and hepatocellular ballooning with or without fibrosis. Because of the complex pathophysiological mechanism and the heterogeneity of NAFLD, including its wide spectrum of clinical and histological characteristics, no specific therapeutic drugs have been approved for NAFLD. The heterogeneity of NAFLD is closely associated with cellular plasticity, which describes the ability of cells to acquire new identities or change their phenotypes in response to environmental stimuli. The liver consists of parenchymal cells including hepatocytes and cholangiocytes and nonparenchymal cells including Kupffer cells, hepatic stellate cells, and endothelial cells, all of which have specialized functions. This heterogeneous cell population has cellular plasticity to adapt to environmental changes. During NAFLD progression, these cells can exert diverse and complex responses at multiple levels following exposure to a variety of stimuli, including fatty acids, inflammation, and oxidative stress. Therefore, this review provides insights into NAFLD heterogeneity by addressing the cellular plasticity and metabolic adaptation of hepatocytes, cholangiocytes, hepatic stellate cells, and Kupffer cells during NAFLD progression.

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Section: Parenchymal Cells: Cholangiocytesmentioning

confidence: 99%

Section: Parenchymal Cells: Cholangiocytesmentioning

confidence: 99%

Cellular heterogeneity and plasticity during NAFLD progression

Park

Choi

Kim

et al. 2023

Front. Mol. Biosci.

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“…Indeed, several models have confirmed that, in the case of impaired hepatocyte regeneration, a response is established that significantly increases the percentage of hepatocytes derived from cholangiocytes, which enables the regenerative process to be correctly completed [ 114 ]. The intrinsic plasticity that hepatocytes and cholangiocytes display facilitates the trans-differentiation process, so that one cell type can make up for the lack of the other and vice versa [ 115 , 116 , 117 ].…”

Section: Molecular Mechanisms Of Liver Regenerationmentioning

confidence: 99%

Liver Regeneration and Immunity: A Tale to Tell

Di-Iacovo

Pieroni

Piobbico

et al. 2023

IJMS

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The physiological importance of the liver is demonstrated by its unique and essential ability to regenerate following extensive injuries affecting its function. By regenerating, the liver reacts to hepatic damage and thus enables homeostasis to be restored. The aim of this review is to add new findings that integrate the regenerative pathway to the current knowledge. An optimal regeneration is achieved through the integration of two main pathways: IL-6/JAK/STAT3, which promotes hepatocyte proliferation, and PI3K/PDK1/Akt, which in turn enhances cell growth. Proliferation and cell growth are events that must be balanced during the three phases of the regenerative process: initiation, proliferation and termination. Achieving the correct liver/body weight ratio is ensured by several pathways as extracellular matrix signalling, apoptosis through caspase-3 activation, and molecules including transforming growth factor-beta, and cyclic adenosine monophosphate. The actors involved in the regenerative process are numerous and many of them are also pivotal players in both the immune and non-immune inflammatory process, that is observed in the early stages of hepatic regeneration. Balance of Th17/Treg is important in liver inflammatory process outcomes. Knowledge of liver regeneration will allow a more detailed characterisation of the molecular mechanisms that are crucial in the interplay between proliferation and inflammation.

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“…However, the relative contribution of activated LPC/OC to parenchymal regeneration remains controversial. Dynamics of hepatocyte‐biliary epithelial cell fate decisions have been reported during liver regeneration (Michalopoulos and Khan 2015; Reid 2015; Kopp et al 2016, Sahoo et al 2022). Lineage tracing techniques in mice and zebrafish have yielded conflicting results regarding the LPC/OC’s effect on regeneration (Furuyama et al 2011, Espanol‐Suner et al 2012, Choi et al 2014, He et al 2014, Rodrigo‐Torres et al 2014, Schaub et al 2014, Tarlow et al 2014, Yanger et al 2014, Font‐Burgada et al 2015, Jors et al 2015, Lu et al 2015, Raven et al 2017).…”

Section: Ccns In Lpc During Development and Liver Regenerationmentioning

confidence: 99%

Significance of CCNs in liver regeneration

Barkin

Jin-Smith

Török

et al. 2023

J. Cell Commun. Signal.

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The liver has an inherent regenerative capacity via hepatocyte proliferation after mild‐to‐modest damage. When hepatocytes exhaust their replicative ability during chronic or severe liver damage, liver progenitor cells (LPC), also termed oval cells (OC) in rodents, are activated in the form of ductular reaction (DR) as an alternative pathway. LPC is often intimately associated with hepatic stellate cells (HSC) activation to promote liver fibrosis. The Cyr61/CTGF/Nov (CCN) protein family consists of six extracellular signaling modulators (CCN1–CCN6) with affinity to a repertoire of receptors, growth factors, and extracellular matrix proteins. Through these interactions, CCN proteins organize microenvironments and modulate cell signalings in a diverse variety of physiopathological processes. In particular, their binding to subtypes of integrin (αvβ5, αvβ3, α6β1, αvβ6, etc.) influences the motility and mobility of macrophages, hepatocytes, HSC, and LPC/OC during liver injury. This paper summarizes the current understanding of the significance of CCN genes in liver regeneration in relation to hepatocyte‐driven or LPC/OC‐mediated pathways. Publicly available datasets were also searched to compare dynamic levels of CCNs in developing and regenerating livers. These insights not only add to our understanding of the regenerative capability of the liver but also provide potential targets for the pharmacological management of liver repair in the clinical setting.

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Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration

Cited by 11 publications

References 76 publications

Cellular heterogeneity and plasticity during NAFLD progression

Cellular heterogeneity and plasticity during NAFLD progression

Liver Regeneration and Immunity: A Tale to Tell

Significance of CCNs in liver regeneration

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