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. 2004 Feb;15(2):649-56.
doi: 10.1091/mbc.e03-06-0432. Epub 2003 Dec 2.

Gene expression in the normal adult human kidney assessed by complementary DNA microarray

John P T Higgins  1 , Lingli Wang, Neeraja Kambham, Kelli Montgomery, Veronica Mason, Stefanie U Vogelmann, Kevin V Lemley, Patrick O Brown, James D Brooks, Matt van de Rijn
Affiliations

Gene expression in the normal adult human kidney assessed by complementary DNA microarray

John P T Higgins et al. Mol Biol Cell. 2004 Feb.

Abstract

The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied gene expression in dissected renal lobes of five adult human kidneys using cDNA microarrays representing approximately 30,000 different human genes. Total RNA was isolated from sections of the inner and outer cortex, inner and outer medulla, papillary tips, and renal pelvis and from glomeruli isolated by sieving. The results revealed unique and highly distinctive patterns of gene expression for glomeruli, cortex, medulla, papillary tips, and pelvic samples. Immunohistochemical staining using selected antisera confirmed differential expression of several cognate proteins and provided histological localization of expression within the nephron. The distinctive patterns of gene expression in discrete portions of the kidney may serve as a resource for further understanding of renal physiology and the molecular and cellular organization of the nephron.

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Figures

Figure 1.
Figure 1.
Unsupervised hierarchical cluster. A representation of the variation in expression of 1548 genes in different compartments of five kidneys. Each row represents a single gene. Each column represents a single sample. Green squares indicate transcript levels below the mean; black squares, transcript levels equal to the mean; red squares, transcript levels greater than the mean; gray squares, technically inadequate or missing data. Gene filtering criteria were for fourfold variation from the normalized mean and at least 80% well-measured spots. Colored bars adjacent to the clustering table indicate the position of the enlarged images. The color of the bar indicates the type of sample in which the cluster of genes is expressed. Red, pelvis cluster; dark blue, papillary tip cluster; brown, tubular cluster; green medullary cluster; turquoise, glomerular cluster; and orange, cortex cluster. Selected gene names are shown. The full dataset can be explored on the accompanying website: https://www.med.stanford.edu/jhiggins/Normal_Kidney/index.shtml. Original magnification: left panel, 5×; right panel, 10×.
Figure 2.
Figure 2.
Isolation of glomeruli from fresh renal cortex shows a high degree of purification. Original magnification: left panel, 5×; right panel, 10×.
Figure 3.
Figure 3.
Correlation of mRNA with protein expression by immunohistochemistry. mRNA expression levels for three genes, SFRP1, keratin 19, and S100P, have been taken from Figure 1 together with the Figure 1 sample dendrogram. Immunohistochemical stains for each of these genes are shown below the mRNA data. Left panel: a full thickness section of a normal renal lobe; right panel: a high-power image taken from the area with the most intense staining. In each case, mRNA expression data correlates with the distribution of the cognate protein by immunohistochemistry. Original magnification: left panel, 5×; right panel, 10×.
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