What Type of Cells Are Hepatocytes? Understanding Liver Epithelial Cells

Hepatocytes represent 70% of the liver cells, which underscores their essential role in liver function. Hepatocytes play a key role in metabolism, detoxification, and regeneration. Their unique structure and remarkable adaptability enable them to efficiently filter toxins, produce essential biomolecules, and repair liver damage.

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What Are Hepatocytes and Where Are They Exactly Found?

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Hepatocytes are the primary functional cells of the liver, comprising approximately 80% of its mass. They play a crucial role in the organ’s metabolic, detoxification, and regenerative functions. 

So, where exactly are hepatocytes found? These highly specialized epithelial cells are located within the hexagonal structures of the liver, called lobules, which form the functional units of the organ. Each lobule is surrounded by the portal triad, a grouping of the hepatic artery, portal vein, and bile duct. Hepatocytes occupy the space between the central vein and the portal triad, enabling them to exchange substances with blood and bile, which is essential for liver function.

Each lobule is divided into three zones (zone 1 or periportal, zone 2 or midzonal, and zone 3 or pericentral) along the porto-central axis. Hepatocytes in each zone perform distinct metabolic tasks based on their location and the oxygen and nutrient gradients they encounter. For example, periportal hepatocytes are more active in processes like gluconeogenesis and amino acid catabolism, while pericentral hepatocytes specialize in glycolysis and biotransformation.

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Hepatocytes exhibit significant diversity in size, ploidy, and gene expression. In humans, hepatocyte size typically ranges from 20 to 30 micrometers, although this can vary depending on their zonal location and metabolic function. Interestingly, many hepatocytes are polyploid, a characteristic that increases with age and can impact their regenerative and metabolic capacity. This structural and functional diversity enables hepatocytes to dynamically adapt to changes in physiological demand, injury, or disease. 

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Are Hepatocytes Epithelial Cells? Understanding Their Structure and Role

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A common question that arises is, are hepatocytes epithelial cells? The answer is yes. Hepatocytes are classified as specialized epithelial cells due to their distinct structure and function. They are unique in their ability to simultaneously perform exocrine and endocrine functions.

Hepatocytes exhibit distinct polarity, with separate basolateral and apical domains. The basolateral side interacts with blood in the liver’s sinusoids, facilitating the uptake of nutrients and toxins. On the other hand, the apical side faces bile canaliculi, where bile acids and waste products are secreted. This dual functionality underscores their role as both secretory and absorptive cells.

One of the most remarkable aspects of hepatocytes is their metabolic versatility. Hepatocytes are crucial for maintaining blood sugar levels through gluconeogenesis and glycogen storage. They also synthesize essential proteins such as albumin and clotting factors, as well as cholesterol and bile acids. Furthermore, hepatocytes are essential for detoxification, employing the cytochrome P450 enzyme system to process drugs and toxins.

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The Regenerative Capacity of Hepatocytes: How They Repair Liver Damage

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The liver’s exceptional regenerative capacity is a hallmark of its functionality, and hepatocytes play a central role in this process. This process is governed by a complex interplay of cellular signaling pathways, zonal organization, and the inherent plasticity of hepatocytes.

Hepatocyte regeneration starts with the capacity of these cells to re-enter the cell cycle when needed. Following liver injury, hepatocytes proliferate to replace lost cells, all while maintaining the organ’s crucial metabolic and detoxification functions. Hepatocytes in zone 2, located in the midzonal region of the liver lobule, display the highest proliferative potential under both homeostatic and regenerative conditions. This suggests a division of labor among hepatocytes, with midzonal cells balancing both metabolism and proliferation. However, hepatocytes from zone 1, which may be derived from bile ducts, those expressing high levels of telomerase, and pericentral hepatocytes expressing Axin2, have also been identified as playing a role in hepatocyte renewal during homeostasis. 

Additionally, hepatocyte plasticity significantly contributes to the liver’s regenerative abilities. In response to severe injury scenarios, hepatocytes can transdifferentiate into other cell types, such as biliary epithelial cells, and vice versa. This remarkable flexibility allows the liver to adapt and repair even in cases where one cell population is severely damaged. For example, biliary epithelial cells can transdifferentiate into zone 1 hepatocytes when chronic injury or senescence limits hepatocyte proliferation.  

Despite the liver’s remarkable ability to regenerate, chronic liver diseases and persistent injuries can impair this process, leading to fibrosis, cirrhosis, or even liver failure. Understanding the regenerative dynamics of hepatocytes is essential for developing therapeutic strategies aimed at enhancing liver repair, especially in conditions where natural regeneration is insufficient.

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References

Chen F, Schönberger K, Tchorz JS. Distinct hepatocyte identities in liver homeostasis and regeneration. JHEP Rep. 2023 Apr 24;5(8):100779. doi: 10.1016/j.jhepr.2023.100779.

Schulze RJ, Schott MB, Casey CA, Tuma PL, McNiven MA. The cell biology of the hepatocyte: A membrane trafficking machine. J Cell Biol. 2019 Jul 1;218(7):2096-2112. doi: 10.1083/jcb.201903090

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