The liver cell type enriched transcriptome
The liver is the largest internal organ in the body and has a wide variety of functions, including metabolization of harmful toxic substances, production and secretion of bile, synthesis and regulation of many plasma proteins, vitamins and hormones, and decomposition and clearance of dead erythroid cells.
2397 genes were predicted to have cell type specificity in the liver.
Liver cell type enriched transcriptome: Summary
Genes with predicted cell type specificity within liver are detailed in Table 1. Identified genes are subdivided into 3 specificity categories, based on the difference between the enrichment score in the corresponding cell type, compared to the other cell types profiled in the tissue (see Methods Summary page for details):
Liver cell type enriched transcriptome: Illustrative examples
Hepatocytes make up 80% of the liver by volume, and are responsible for a large number of essential physiological functions, including metabolism, detoxification and transformation of foreign substances, which involves metabolic enzymes such as Glycine-N-acyltransferase (GLYAT) and Dimethylglycine dehydrogenase (DMGDH), and production and secretion of bile, which involves proteins such as Solute carrier family 27 member 5 (SLC27A5) and Cytochrome P450 family 27 subfamily A member 1 (CYP27A1). Another important function of hepatocytes is the synthesis and homeostatic regulation of plasma proteins, such as the Complement component 4 binding protein alpha (C4BPA) and serum amyloid P component (APCS).
Bile production proteins
Cholangiocytes line the bile ducts, which are located within the portal triad alongside the portal vein and arteries. Bile ducts transport bile created by the hepatocytes towards the gallbladder, where it is concentrated and stored until required, when it is secreted into the small intestine to assist in digestion of lipids. Several epithelial genes typical of glandular like epithelia were classified as having specificity in cholangiocytes, such as the intermediate filament keratin 19 (KRT19) and the transcription factor SRY-box transcription factor 9 (SOX9).
Hepatic stellate cells (Ito cells)
Hepatic stellate cells, also known as Ito cells, are fibroblast-like cells located within the space of Disse, between hepatocytes and the sinusoidal endothelium. When quiescent, they are one of the body's primary storage points of vitamin A in lipid filled droplets. Upon inflammatory activation, they can transform into myo-fibroblast like cells, expressing smooth muscle proteins and producing large quantities of extracellular matrix proteins such as collagen, contributing heavily to liver fibrosis. Genes classified as having specificity in hepatic stellate cells include the proteoglycan decorin (DCN), which plays a role in collagen fibril assembly, and elastin microfibril interfacer 1 (EMILIN1), which assists in cell adhesion to elastic fibers.
NK cells, or Natural Killer cells, share many enriched genes with T-cells, and are an immune cell type important for detection and elimination of both virus-infected cells, as well as tumor transformed or stressed cells. NK cells are especially abundant in the liver, making up 50% of the resident lymphocyte population according to some estimates. NK cells can recognize abnormal cells via both activating and inhibitory receptor protein complexes, and respond by releasing cytotoxic granules that destroy the target cells. Genes classified as having specificity in liver NK cells include the Killer cell lectin like receptor K1 (KLRK1), which helps recognize stressed or malignant cells, and the cytotoxic granzyme B (GZMB), which can induce apoptosis in target cells.
Erythroid cells, also known as red blood cells, are nucleus-free cells that deliver oxygen around the body, bound to the hemoglobin molecules that give the cell, and the blood, its distinctive red color. The liver, along with the spleen, is one of the primary sites of erythroid cell recycling, where aging erythroid cells are phagocytosed by Kupffer cells and the essential components of the heme molecules are re-used, the iron is released and eventually used to make new heme molecules, while the rest of the heme eventually forms bilirubin, which is a component of bile. Genes classified as having specificity in erythroid cells include the actin binding protein Spectrin alpha, erythrocytic 1 (SPTA1), and hemoglobin subunit alpha 1 (HBA1).
Sinusoidal endothelial cells
Sinusoidal endothelial cells are an endothelial subtype specific to the liver that line the sinusoidal space. Characterized by their unusual fenestrated morphology and discontinuous arrangement, sinusoidal endothelial cells are also notable for their expression of high levels of immune recognition and phagocytosis related proteins, and lower levels of cell junctional and basement membrane proteins compared to other endothelium. Genes classified as having specificity in the sinusoidal endothelium include the pattern recognition receptor C-type lectin domain family 4 member G (CLEC4G), and the class B scavenger receptor (CD36).
Kupffer cells (Macrophages)
Resident macrophages are found in almost all tissues, and are responsible for monitoring tissues for potential pathogens or other harmful molecules. Upon activation they can phagocytose pathogens, as well as debris from dead or dying cells, and can present antigens from phagocytosed material towards the adaptive immune system by displaying on MHC class II proteins. They can also aid during wound healing and tissue repair.
Kupffer cells are the specialized resident macrophages within the liver. Their location within the liver sinusoids makes them especially important as one of the first immune lines of defense against potentially harmful material absorbed from the gut, delivered via the bloodstream directly to the liver via the hepatic portal vein. They also play a role in the clearance of dead erythroid cells. Genes classified as having specificity in Kupffer cells include allograft inflammatory factor 1 (AIF1), which plays a role in Kupffer cell migration, and the pattern recognition receptor (CD180).