title: Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas.
abstract: We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increased the total number of islets. β cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the β cell expansion was attributable to proliferation of pre-existing β cells. At sufficiently high Ngn3 expression level, upto 14% of all β cells and 40% of small islet β cells derived from non-β cells. Moreover, β cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing β cells supporting a key role for Ngn3(+) insulin(-) cells in β cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed β cells as well as reprogramming of non-β cells contribute to in vivo β cell expansion in the injured pancreas of adult mice.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Van de Casteele
authors.forename: G
authors.initials: G
authors.lastname: Leuckx
authors.forename: L
authors.initials: L
authors.lastname: Baeyens
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: Y
authors.initials: Y
authors.lastname: Yuchi
authors.forename: V
authors.initials: V
authors.lastname: Coppens
authors.forename: S
authors.initials: S
authors.lastname: De Groef
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.forename: C
authors.initials: C
authors.lastname: Svensson
authors.forename: U
authors.initials: U
authors.lastname: Ahlgren
authors.forename: J
authors.initials: J
authors.lastname: Ahnfelt-Rønne
authors.forename: O D
authors.initials: OD
authors.lastname: Madsen
authors.forename: A
authors.initials: A
authors.lastname: Waisman
authors.forename: Y
authors.initials: Y
authors.lastname: Dor
authors.forename: J N
authors.initials: JN
authors.lastname: Jensen
authors.forename: H
authors.initials: H
authors.lastname: Heimberg
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D048429:Cell Size; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C407737:Neurog3 protein, mouse