β细胞可由成年小鼠受损胰腺中的内源性祖细胞生成。

Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas.

作者信息

Xu Xiaobo, D'Hoker Joke, Stangé Geert, Bonné Stefan, De Leu Nico, Xiao Xiangwei, Van de Casteele Mark, Mellitzer Georg, Ling Zhidong, Pipeleers Danny, Bouwens Luc, Scharfmann Raphael, Gradwohl Gerard, Heimberg Harry

机构信息

Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B1090 Brussels, Belgium.

出版信息

Cell. 2008 Jan 25;132(2):197-207. doi: 10.1016/j.cell.2007.12.015.

DOI:10.1016/j.cell.2007.12.015

PMID:18243096

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.

摘要

糖尿病治疗的新策略显然会受益于β细胞干细胞/祖细胞的应用。然而，成体β细胞祖细胞是否存在是当今糖尿病研究中最具争议的问题之一。在胚胎发育中最早的胰岛细胞特异性转录因子神经生成素3（Ngn3）表达的引导下，我们发现β细胞祖细胞可在成年小鼠受损胰腺中被激活，且位于导管内衬。成体祖细胞的分化依赖于Ngn3，并产生所有胰岛细胞类型，包括葡萄糖反应性β细胞，这些β细胞随后会在原位以及在胚胎胰腺外植体中培养时增殖。因此，成年小鼠胰腺中存在多能祖细胞，并且可以通过细胞自主激活，通过分化和增殖而非仅通过已有β细胞的自我复制来增加功能性β细胞数量。