In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
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DOI：
10.1038/nature07314
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发表时间：
2008-10-02
影响因子：
6.7
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中科院分区：
文献类型：
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再生医学的一个目标是将成人细胞转化为其他类型的细胞，以进行组织修复和再生。尽管成体细胞重新编程的个别例子是已知的，但对于如何以受控的方式将一种细胞类型转变为另一种细胞类型，还没有普遍的理解。在这里，使用体内重新表达关键发育调节因子的策略，我们确定了三种转录因子(Ngn3、Pdx1和MafA)的特定组合，它们可以将成年动物分化的胰腺外分泌细胞重新编程为与β细胞非常相似的细胞。诱导的β-细胞在大小、形态和超微结构上与内源性胰岛β-细胞无明显区别。它们表达β细胞功能所必需的基因，并能通过重塑局部血管和分泌胰岛素来改善高血糖。这项研究提供了一个在成人器官中使用定义的因子进行细胞重编程的例子，并提出了一个指导成人细胞重编程而不会回复到多能干细胞状态的一般范例。
One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3, Pdx1 and MafA) that reprogram differentiated pancreatic exocrine cells in adult animals into cells that closely resemble β-cells. The induced β-cells are indistinguishable from endogenous islet β-cells in size, shape, and ultrastructure. They express genes essential for β-cell function and can ameliorate hyperglycemia by remodeling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing adult cell reprogramming without reversion to a pluripotent stem cell state.