A panoramic view of gene expression in the human kidney.
To gain a molecular understanding of kidney functions, we established a high-resolution map of gene expression patterns in the human kidney. The glomerulus and seven different nephron segments were isolated by microdissection from fresh tissue specimens, and their transcriptome was characterized by using the serial analysis of gene expression (SAGE) method. More than 400,000 mRNA SAGE tags were sequenced, making it possible to detect in each structure transcripts present at 18 copies per cell with a 95% confidence level. Expression of genes responsible for nephron transport and permeability properties was evidenced through transcripts for 119 solute carriers, 84 channels, 43 ion-transport ATPases, and 12 claudins. Searching for differences between the transcriptomes, we found 998 transcripts greatly varying in abundance from one nephron portion to another. Clustering analysis of these transcripts evidenced different extents of similarity between the nephron portions. Approximately 75% of the differentially distributed transcripts corresponded to cDNAs of known or unknown function that are accurately mapped in the human genome. This systematic large-scale analysis of individual structures of a complex human tissue reveals sets of genes underlying the function of well-defined nephron portions. It also provides quantitative expression data for a variety of genes mutated in hereditary diseases and helps in sorting candidate genes for renal diseases that affect specific portions of the human nephron.
Département de Biologie Joliot-Curie, Service de Biochimie et de Génétique Moléculaire, Commissariat à l'Energie Atomique Saclay, 91191 Gif-sur-Yvette Cedex, France.
Danielle
D
Chabardès-Garonne
Arnaud
A
Mejéan
Jean-Christophe
JC
Aude
Lydie
L
Cheval
Antonio
A
Di Stefano
Marie-Claude
MC
Gaillard
Martine
M
Imbert-Teboul
Monika
M
Wittner
Chanth
C
Balian
Véronique
V
Anthouard
Catherine
C
Robert
Beatrice
B
Ségurens
Patrick
P
Wincker
Jean
J
Weissenbach
Alain
A
Doucet
Jean-Marc
JM
Elalouf
D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008953:Models, Anatomic; D008969:Molecular Sequence Data; D009399:Nephrons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012984:Software
D018076:DNA, Complementary; D012333:RNA, Messenger