The kidney cell type enriched transcriptome
The kidneys are specialized organs that regulate body homeostasis, predominantly by controlling the contents of urine that is excreted from the body. Waste products such as urea and foreign substances such as toxins and drugs are filtered from the blood and excreted in the urine, and the kidney can also regulate the blood volume and composition by adjusting the amount of water and electrolytes that are excreted or reabsorbed along the nephron. The kidney is also the source of several essential hormones such as catalyzing vitamin D activation, production of renin, which activates the angiotensin pathway, important in regulation of blood pressure, and erythropoietin, which stimulates erythroid cell production.
The human kidney contains around 1 million subunits known as nephrons. At the head of each nephron blood plasma is filtered in the glomerulus under high pressure, and the ultrafiltrate is passed to the renal tubule. The renal tubule facilitates the reabsorption of water and essential molecules that are not intended to be excreted. Eventually the filtrate passes into the collecting ducts which empty into the bladder to form urine.
1780 genes were predicted to have cell type specificity in the kidney.
Kidney cell type enriched transcriptome: Summary
Genes with predicted cell type specificity within kidney 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):
Kidney cell type enriched transcriptome: Illustrative examples
Podocytes are epithelial cells with long interlocking foot processes that wrap around the capillaries in the glomerulus. The small gaps between the cells are called slit diaphragms, and are permeable to water, ions and small molecules such as urea, which can enter the glomerular filtrate freely, but impermeable to cells and most proteins, which remain in the blood. Genes classified as having specificity in podocytes include the growth factor and angiogenesis inducer Fibroblast growth factor 1 (FGF1), and less well known Rho GTPase activating protein 28 (ARHGAP28).
Proximal tubular cells
The proximal tubule is the earliest portion of the renal tubule the filtrate enters after leaving the glomerulus, and is the site of the majority of reabsorption of organic molecules (such as glucose and amino acids), as well as electrolytes such as sodium, potassium, phosphate and bicarbonate. Certain organic molecules are also selectively secreted into the proximal tubule. Proximal tubule cells are extremely metabolically active and contain many active transport proteins dedicated to the selective reabsorption and secretion of specific molecules, and are covered in numerous microvilli to increase the surface area for resorption.
Genes classified as having specificity in proximal tubular cells include solute transporters Solute carrier family 4 member 4 (SLC4A4), which regulates bicarbonate transport and helps maintain the pH of the filtrate, and Solute carrier family 27 member 2 (SLC27A2), which regulates reuptake of fatty acids. Other genes with specificity include Cadherin related family member 5 (CDHR5), which helps control the packing of microvilli at the apical membrane, the metabolic related proteins Aldolase, fructose-bisphosphate B (ALDOB), involved in fructose metabolism and glycolysis, and Glycine-N-acyltransferase (GLYAT), which is involved in detoxification of certain foreign compounds. Also with high proximal tubular specificity are genes with lesser known functions in the kidney such as APOBEC1 complementation factor (A1CF), an RNA binding protein which assists in mRNA modification.
Proximal tubule 1
Proximal tubule 2
Ascending loop of Henle cells
The loop of Henle is the primary site for reabsorption of water from the renal filtrate. The cells of the ascending limb have very low permeability for water, but contain large numbers of ion pumps to reabsorb sodium, potassium, calcium, magnesium and chloride ions from the filtrate. This creates a strong osmotic gradient in the extracellular space, leading to significant reabsorption or water in the descending limb. Genes classified as having specificity in the ascending loop of Henle include Claudin 16 (CLDN16), which regulates magnesium ion resorption, Calcium sensing receptor (CASR), which regulates calcium resorption, as well as Potassium inwardly rectifying channel subfamily J member 1 (KCNJ1), which is involved in potassium resorption.
The intercalated cells are located in the collecting duct, and act to regulate the pH of the urine by selectively secreting or reabsorbing hydrogen and bicarbonate ions. Intercalated cells can be subdivided into type A and type B, which work in tandem with opposing effects in order to maintain the homeostasis of the urine's pH. Type A intercalated cells secrete hydrogen ions and reabsorb bicarbonate, increasing acidity of the urine, whereas type B intercalated cells secrete bicarbonate and reabsorb hydrogen ions, reducing urine acidity. Solute carrier family 4 member 1 (SLC4A1) is an important protein in type A intercalated cells, which directly resorbs bicarbonate from the urine in exchange for chloride ions. whereas Solute carrier family 26 member 4 (SLC26A4), also known as pendrin, has almost the opposite function in type B intercalated cells, secreting bicarbonate into the urine in exchange for chloride ions. Other genes classified as having specificity in intercalated cells include the ammonium transporter Rh family C glycoprotein (RHCG), as well as Transmembrane protein 52B (TMEM52B), which has unknown function.