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Articleβ Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas
Xiaobo Xu,1,5 Joke D'Hoker,1,5 Geert Stangé,1,5 Stefan Bonné,1,5 Nico De Leu,1,5 Xiangwei Xiao,1,5 Mark Van De Casteele,1,5 Georg Mellitzer,2,5 Zhidong Ling,1,5 Danny Pipeleers,1,5 Luc Bouwens,1,5 Raphael Scharfmann,3,4,5 Gerard Gradwohl,2,4,5 and Harry Heimberg1,4,5,
1 Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B1090 Brussels, Belgium
2 INSERM, U682, Development and Physiopathology of the Intestine and Pancreas, 67200 Strasbourg, France
3 INSERM, U845, Faculty of Medicine Necker, 75730 Paris, France
4 Beta Cell Biology Consortium, 2213 Garland Avenue, 9465 MRB IV, Nashville, TN 37323-0494, USA
5 JDRF Center for Beta Cell Therapy in Diabetes, Laarbeeklaan 103, B1090 Brussels, Belgium
Corresponding author
Harry Heimberg
Novel strategies in diabetes therapy would obviously benefit from the use of beta (β) cell stem/progenitor cells. However, whether or not adult β cell progenitors exist is one of the most controversial issues in today's diabetes research. Guided by the expression of Neurogenin 3 (Ngn3), the earliest islet cell-specific transcription factor in embryonic development, we show that β cell progenitors can be activated in injured adult mouse pancreas and are located in the ductal lining. Differentiation of the adult progenitors is Ngn3 dependent and gives rise to all islet cell types, including glucose responsive β cells that subsequently proliferate, both in situ and when cultured in embryonic pancreas explants. Multipotent progenitor cells thus exist in the pancreas of adult mice and can be activated cell autonomously to increase the functional β cell mass by differentiation and proliferation rather than by self-duplication of pre-existing β cells only.
