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Diabetes 52:2503-2512, 2003
© 2003 by the American Diabetes Association, Inc.

Nestin-Lineage Cells Contribute to the Microvasculature but Not Endocrine Cells of the Islet

Mary Kay Treutelaar1, Jennifer M. Skidmore2, Claudia L. Dias-Leme1, Manami Hara3, Lizhi Zhang4, Diane Simeone4, Donna M. Martin2,5, and Charles F. Burant1

1 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
2 Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan
3 Department of Medicine, University of Chicago, Chicago, Illinois
4 Department of Surgery, University of Michigan, Ann Arbor, Michigan
5 Department of Human Genetics, University of Michigan, Ann Arbor, Michigan

To clarify the lineage relationship between cells that express the neural stem cell marker nestin and endocrine cells of the pancreas, we analyzed offspring of a cross between mice carrying a nestin promoter/enhancer-driven cre-recombinase (Nestin-cre) and C57BL/6J-Gtrosa26tm1Sor mice that carry a loxP-disrupted ß-galactosidase gene (Rosa26). In nestin-cre+/tg;R26RloxP/+ embryos, cre-recombinase was detected in association with nestin-positive cells in the pancreatic mesenchyme with some of the nestin-positive cells lining vascular channels. In postnatal mice, pancreatic ß-galactosidase expression was restricted to vascular endothelial cells of the islet and a subset of cells in the muscularis of arteries in a distribution identical to endogenous nestin expression. Ex vivo explants of mouse pancreatic ducts grew dense cultures that costained for nestin and ß-galactosidase, demonstrating recombination in vitro. The cultures could be differentiated into complex stereotypic structures that contain nestin- and insulin-expressing cells. Nestin-cre+/tg;R26RloxP/+-derived duct cultures showed that insulin-positive cells were negative for ß-galactosidase. These results indicate that both in vivo and in vitro pancreatic endocrine cells arise independently of nestin-positive precursors. The apparent vascular nature of the nestin-positive cell population and the close association with endocrine cells suggest that nestin-positive cells play an important role in the growth and maintenance of the islet.


Address correspondence and reprint requests to Charles Burant, MD, University of Michigan Medical Center, Box 0678, 1500 E. Medical Center Dr., Ann Arbor, MI 48109. E-mail: burantc{at}umich.edu


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