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Here, we developed a new model of \u03b2-cell regeneration, combining pancreatic duct ligation (PDL) with elimination of pre-existing \u03b2-cells with alloxan. In this model, in which virtually all \u03b2-cells observed are neogenic, large numbers of \u03b2-cells were generated within 2 weeks. Strikingly, the neogenic \u03b2-cells arose primarily from \u03b1-cells. \u03b1-cell proliferation was prominent following PDL plus alloxan, providing a large pool of precursors, but we found that \u03b2-cells could form from \u03b1-cells by direct conversion with or without intervening cell division. Thus, classical asymmetric division was not a required feature of the process of \u03b1- to \u03b2-cell conversion. Intermediate cells coexpressing \u03b1-cell- and \u03b2-cell-specific markers appeared within the first week following PDL plus alloxan, declining gradually in number by 2 weeks as \u03b2-cells with a mature phenotype, as defined by lack of glucagon and expression of MafA, became predominant. In summary, these data revealed a novel function of \u03b1-cells as \u03b2-cell progenitors. The high efficiency and rapidity of this process make it attractive for performing the studies required to gain the mechanistic understanding of the process of \u03b1- to \u03b2-cell conversion that will be required for eventual clinical translation as a therapy for diabetes.<\/jats:p>","DOI":"10.1002\/stem.482","type":"journal-article","created":{"date-parts":[[2010,7,22]],"date-time":"2010-07-22T15:20:57Z","timestamp":1279812057000},"page":"1630-1638","source":"Crossref","is-referenced-by-count":160,"title":["Pancreatic \u03b2-Cell Neogenesis by Direct Conversion from Mature \u03b1-Cells"],"prefix":"10.1093","volume":"28","author":[{"given":"Cheng-Ho","family":"Chung","sequence":"first","affiliation":[{"name":"Sanford Children's Health Research Center andSanford-Burnham Medical Research Institute, California, USA"},{"name":"Sanford-Burnham Institute Graduate Program, Sanford-Burnham Medical Research Institute, California, USA"},{"name":"Division of Endocrinology and Metabolism, 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