title: Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas.
abstract: Novel strategies in diabetes therapy would obviously benefit from the use of beta (beta) cell stem/progenitor cells. However, whether or not adult beta 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 beta 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 beta 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 beta cell mass by differentiation and proliferation rather than by self-duplication of pre-existing beta cells only.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B1090 Brussels, Belgium.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xu
authors.forename: Joke
authors.initials: J
authors.lastname: D'Hoker
authors.forename: Geert
authors.initials: G
authors.lastname: Stangé
authors.forename: Stefan
authors.initials: S
authors.lastname: Bonné
authors.forename: Nico
authors.initials: N
authors.lastname: De Leu
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Xiao
authors.forename: Mark
authors.initials: M
authors.lastname: Van de Casteele
authors.forename: Georg
authors.initials: G
authors.lastname: Mellitzer
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Ling
authors.forename: Danny
authors.initials: D
authors.lastname: Pipeleers
authors.forename: Luc
authors.initials: L
authors.lastname: Bouwens
authors.forename: Raphael
authors.initials: R
authors.lastname: Scharfmann
authors.forename: Gerard
authors.initials: G
authors.lastname: Gradwohl
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008026:Ligation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D009924:Organ Culture Techniques; D010179:Pancreas / Q000166:cytology* / Q000293:injuries*; D010183:Pancreatic Ducts / Q000601:surgery; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D007328:Insulin; D007633:Keratins; D009419:Nerve Tissue Proteins; D001616:beta-Galactosidase; C407737:Neurog3 protein, mouse