Quantitative Cellular Anatomy of the Rat Kidney

Abstract

The understanding of renal physiology at a cellular level is progressing rapidly as a result of the recent introduction of techniques for measurement of mRNA levels (RNA‐Seq) and protein levels (protein mass spectrometry) in very small samples consisting of single tubules and single cells. An important question is: How can we use single‐cell and single‐tubule data to predict results of analyses carried out at a whole kidney level, e.g. western blotting? The purpose of this work is to estimate the number of each cell type present in renal tubules of a kidney from a typical 250‐g adult rat (from proximal tubule [PT] to inner medullary collecting duct [IMCD]). For this, we used quantitative structural data gleaned from various 20th century publications. These studies identify the length of each tubule segment, the number of nephrons/collecting ducts, the number of cells per mm and the protein content per mm of each renal tubule segment. The calculations account for differing lengths of loops of Henle, junctions in the connecting tubule (CNT) and IMCD, and different populations of nephrons (short‐looped [71%] and long‐looped [29%]). The calculations reveal that the 38,000 nephrons and their collecting ducts have an aggregate length of 840 meters. The total number of cells from PT to IMCD is 207 million of which 52% are PT cells, 17% are thick ascending limb (TAL) cells, 10% are distal convoluted tubule (DCT) cells, 5% are collecting duct intercalated cells (ICs) and 10% are aquaporin‐2‐expressing cells (PCs). The calculations reveal that the total protein mass of all renal tubule epithelial cells is 119 mg or 40% of the dry weight of the kidney. In terms of protein mass, percentage of individual cell types are: PT, 72%; TAL, 10%; DCT, 7%; ICs, 2%; and PCs, 5%. The average protein masses per cell (pg/cell) are: PT, 804; medullary TAL, 402; cortical TAL, 287; DCT, 425; CNT, 288, cortical collecting duct PC, 212 and IMCD, 300. These calculations provide an illustration of how old data can take on a new significance in light of modern systems biology.Support or Funding InformationThis work was supported by the APS 2017 Frontiers Research Community Leader Fellowship to TR.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.