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.
Chabardès-Garonne
Danielle
D
Département de Biologie Joliot-Curie, Service de Biochimie et de Génétique Moléculaire, Commissariat à l'Energie Atomique Saclay, 91191 Gif-sur-Yvette Cedex, France.
Mejéan
Arnaud
A
Aude
Jean-Christophe
JC
Cheval
Lydie
L
Di Stefano
Antonio
A
Gaillard
Marie-Claude
MC
Imbert-Teboul
Martine
M
Wittner
Monika
M
Balian
Chanth
C
Anthouard
Véronique
V
Robert
Catherine
C
Ségurens
Beatrice
B
Wincker
Patrick
P
Weissenbach
Jean
J
Doucet
Alain
A
Elalouf
Jean-Marc
JM
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