Liver zonation

Single-cell transcriptomic profiling of healthy and fibrotic adult zebrafish liver reveals conserved cell identities and stellate cell activation phenotypes with human liver

“…1B, S1E ) these cells appeared to be heterogenous multiplets of hepatocytes and immune cells. Collectively, these data demonstrate that the adult zebrafish liver is comprised of multiple unique hepatocyte populations with distinct functions, similar to the specialization of human hepatocytes (19, 33, 34).…”

“…Although conventional studies have shown that the zebrafish liver is similar to the human liver (10), our comparative analysis using scRNA-seq reveals highly conserved marker genes in like cell types with similar transcriptional profiles indicative of shared identity and functional roles in the liver. While the zebrafish liver is structurally different from the human liver and not known to have architectural zonation (10,33,34), our zebrafish liver scRNA-seq dataset revealed three main, but distinct, groups of hepatocytes enriched for pathways involved in oxidative phosphorylation (zHep1, zHep7, and zHep8), cholesterol, steroid, and lipid metabolism (zHep2, zHep3, zHep4, and zHep5), and fatty acid transport and glucose metabolism (zHep6). Whether these differences are related to the spatial location of these hepatocytes in the zebrafish liver or indicate zonation of the zebrafish liver similar to that of the human liver will require further study and emerging spatial scRNA-seq platforms may be applicable (80).…”

The Synergy between Organ-on-a-Chip and Artificial Intelligence for the Study of NAFLD: From Basic Science to Clinical Research

“…While the functions of non-parenchymal cells span from maintaining the structural organization of the liver (HSC) to regulate exchange with blood (LSEC) and immune response (KC), the function of parenchymal (hepatocytes) is to perform most of the metabolic jobs such as decomposition and synthesis of sugars and fats, ammonia removal and synthesis of bile acids. The place where the hepatocytes are located between the portal triad and central vein is extremely important for the body and it is known as zonation [41]. The environment of the cells closer to portal triad is rich in oxygen and glucose because the cells perform the processes that are more energetically demanding, such as glycolysis, bile acid production and xenobiotic metabolism.…”

“…The environment of the cells closer to portal triad is rich in oxygen and glucose because the cells perform the processes that are more energetically demanding, such as glycolysis, bile acid production and xenobiotic metabolism. The mid-lobule hepatocytes are specialized in modulation of insulin growth factors and iron metabolism while the cells in the proximity of central vein are dedicated to gluconeogenesis, β-oxidation and cholesterol metabolism [41]. The cellular organization of the liver represents an essential factor for the hepatocytes' optimal working condition but, at same time, the most significant challenge for the mimetic tissue engineering.…”

Rappaport, Glisson, Hering, and Mall—Champions of Liver Microanatomy: Microscopic and Ultramicroscopic Anatomy of the Liver Into the Modern Age

“…22), 35 one of the greatest liver anatomists, Hering, whom we have described earlier as “the ultimate student of perception,” could have rendered necessary visual guidance. In this context, attention should be directed to an elegant graphic rendition of liver zonation beyond mere oxygenation, embodied in a so‐called Hepatology Snapshot 36 that comprehensively embraces zonation of hepatocyte metabolic functions (i.e., glycolysis, bile acid production, glutamine synthesis, xenobiotic metabolism, gluconeogenesis, ß‐oxidation, cholesterol biosynthesis, ureagenesis, protein secretion, iron homeostasis, and modulation of insulin growth factors), zonation of the function of nonparenchymal cells (i.e., endothelial, stellate, and Kupffer), and even zonated damage in various liver diseases. Although Rappaport’s complex acinar architecture may not completely encompass the true complexity of the liver, it strikes an important balance, which allows for consistent pathological categorization and further study of liver disease 36 …”