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【Nature】beta细胞 体内再生
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07314.html
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 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling 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 cell reprogramming without reversion to a pluripotent stem cell state. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 这个PI是个牛人
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
通过将胰腺外分泌细胞进行体内基因重组使其转化为β细胞
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 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling 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 cell reprogramming without reversion to a pluripotent stem cell state.
再生医学的目标之一就是将成体细胞转化为有益的其他类型细胞以用于组织的修复与再生。虽然个别成体细胞的基因重组已经有了成功的范例，但通过既定的方法实现一种类型的细胞向另一种类型转化仍然缺乏一个普遍适用的共识。这里，在体内通过一种策略将生长发育中关键的调控因子进行再表达，我们鉴定出了一系列3个转录因子（Ngn3 (亦称 Neurog3) ，Pdx1 和 Mafa），将它们重组入成年小鼠的胰腺外分泌细胞，相应的细胞可分化成类似于β细胞的细胞.这种通过诱导而来的“β细胞”在细胞的大小，形态和超微结构上与真正的胰腺内分泌β细胞无二。它们可表达那些在实现β细胞功能上必须的基因，通过重塑局部的血管系统及分泌胰岛素使高血糖得到缓解。该研究给了我们一个运用特定因素诱导成体器官细胞水平基因重组的成功范例，并实现了一个具有普遍意义的在不依赖多能干细胞的情况下，直接运用细胞基因重组，成功实现细胞类型转化的范例
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作者:admin@医学,生命科学 2010-10-21 05:11
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