Transcriptional Program of the Endocrine Pancreas in Mice and Humans

Transcriptional Program of the Endocrine Pancreas in Mice and Humans Klaus H. Kaestner 1 , Catherine S. Lee 1 , L. Marie Scearce 1 , John E. Brestelli 1 , Athanasios Arsenlis 1 , Phillip Phuc Le 1 , Kristen A. Lantz 1 , Jonathan Crabtree 2 , Angel Pizarro 2 , Joan Mazzarelli 2 , Deborah Pinney 2 , Steve Fischer 2 , Elisabetta Manduchi 2 , Christian J. Stoeckert, Jr. 1 2 , Gerard Gradwohl 3 , Sandra W. Clifton 4 , Juliana R. Brown 5 , Hiroshi Inoue 6 , Corentin Cras-Méneur 6 and M. Alan Permutt 6 1 Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 2 Center for Bioinformatics, University of Pennsylvania, Philadelphia, Pennsylvania 3 INSERM 381, Strasbourg, France 4 Genome Sequencing Center, Washington University, St. Louis, Missouri 5 Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 6 Department of Internal Medicine, Washington University, St. Louis, Missouri Address correspondence and reprint requests to Klaus H. Kaestner, Department of Genetics, University of Pennsylvania, 415 Curie Blvd., Philadelphia, PA 19104. E-mail: kaestner{at}mail.med.upenn.edu Abstract The Endocrine Pancreas Consortium was formed in late 1999 to derive and sequence cDNA libraries enriched for rare transcripts expressed in the mammalian endocrine pancreas. Over the past 3 years, the Consortium has generated 20 cDNA libraries from mouse and human pancreatic tissues and deposited >150,000 sequences into the public expressed sequence tag databases. A special effort was made to enrich for cDNAs from the endocrine pancreas by constructing libraries from isolated islets. In addition, we constructed a library in which fetal pancreas from Neurogenin 3 null mice, which consists of only exocrine and duct cells, was subtracted from fetal wild-type pancreas to enrich for the transcripts from the endocrine compartment. Sequence analysis showed that these clones cluster into 9,464 assembly groups (approximating unique transcripts) for the mouse and 13,910 for the human sequences. Of these, >4,300 were unique to Consortium libraries. We have assembled a core clone set containing one cDNA for each assembly group for the mouse and have constructed the corresponding microarray, termed “PancChip 4.0,” which contains >9,000 nonredundant elements. We show that this PancChip is highly enriched for genes expressed in the endocrine pancreas. The mouse and human clone sets and corresponding arrays will be important resources for diabetes