Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
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DOI：
10.1038/nature02520
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发表时间：
2004-05-06
期刊：
影响因子：
64.8
通讯作者：
Melton, DA
中科院分区：
文献类型：
--
作者：
Dor, Y;Brown, J;Melton, DA
组织如何产生和维持正确的细胞数量是生物学中的一个基本问题。原则上，组织周转可以通过干细胞的分化发生，正如血液、皮肤和肠道的充分证明，或通过复制现有的分化细胞。最近对成体干细胞的研究突出了它们对器官维护和修复的潜在贡献。然而，干细胞在体内实际参与这些过程的程度尚不清楚。在这里，我们介绍了一种遗传谱系追踪的方法，以确定干细胞对感兴趣组织的贡献。我们关注的是胰岛β细胞，其出生后的起源仍然存在争议。我们的分析表明，在小鼠成年后和胰腺切除后，新的β细胞的主要来源是预先存在的β细胞，而不是多能干细胞。这些结果表明，终末分化的β细胞在体内保持着显著的增殖能力，并对成年干细胞在β细胞补充中发挥重要作用的观点提出了质疑。
How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic beta-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment.