Nature Biotechnology
22, 1115 - 1124 (2004)
Published online: 22 August 2004; | doi:10.1038/nbt1004
Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineagesRaewyn M Seaberg1, 6, Simon R Smukler1, 6, Timothy J Kieffer2, Grigori Enikolopov3, Zeenat Asghar4, Michael B Wheeler4, Gregory Korbutt5
& Derek van der Kooy11
Department of Medical Genetics and Microbiology, University of Toronto, Toronto M5S 1A8, Canada. 2
Department of Physiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. 3
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. 4
Department of Physiology, University of Toronto, Toronto M5S 1A8, Canada. 5
Department of Surgery & Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2N8, Canada. 6
These authors contributed equally to this work.
Correspondence should be addressed to Raewyn M Seaberg raewyn.seaberg@utoronto.caThe clonal isolation of putative adult pancreatic precursors has been an elusive goal of researchers seeking to develop cell replacement strategies for diabetes. We report the clonal identification of multipotent precursor cells from the adult mouse pancreas. The application of a serum-free, colony-forming assay to pancreatic cells enabled the identification of precursors from pancreatic islet and ductal populations. These cells proliferate in vitro to form clonal colonies that coexpress neural and pancreatic precursor markers. Upon differentiation, individual clonal colonies produce distinct populations of neurons and glial cells, pancreatic endocrine  -,  - and  -cells, and pancreatic exocrine and stellate cells. Moreover, the newly generated -like cells demonstrate glucose-dependent Ca2+ responsiveness and insulin release. Pancreas colonies do not express markers of embryonic stem cells, nor genes suggestive of mesodermal or neural crest origins. These cells represent a previously unidentified adult intrinsic pancreatic precursor population and are a promising candidate for cell-based therapeutic strategies.
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