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Lineage tracing evidence for in-vitro dedifferentiation, but rare proliferation, of mouse pancreatic ß cells

¹Department of Cellular Biochemistry and Human Genetics, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
²Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel

Correspondence: dor{at}md.huji.ac.il

Understanding and manipulating pancreatic ß-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human ß cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to redifferentiate into ß cells. To directly test if cultured ß cells dedifferentiate we applied genetic lineage tracing in mice. Differentiated ß cells were heritably labeled using the Cre-lox system, and their fate in culture was followed. We provide evidence that mouse ß cells can indeed undergo dedifferentiation in vitro into an insulin-, pdx1- and glut2-negative state. However, dedifferentiated ß cells only rarely proliferate under standard culture conditions and are eventually eliminated from cultures. Thus, the predominant mesenchymal cells seen in cultures of mouse islets are not of a ß-cell origin.

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