Cells keep a memory of their tissue origin during axolotl limb regeneration

Cells keep a memory of their tissue origin during axolotl limb regeneration
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DOI:
10.1038/nature08152
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发表时间:
2009-07-02
期刊:
影响因子:
64.8
通讯作者:
Tanaka, Elly M.
Tanaka, Elly M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kragl, Martin;Knapp, Dunja;Tanaka, Elly M.

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在肢体再生过程中,成人组织转化为一个称为芽基的未分化祖细胞区域,该区域重新形成肢体的各种组织。以前的实验已经导致广泛接受肢体组织去分化形成多能细胞。在这里,我们已经重新审视这个问题,使用整合的GFP转基因,以跟踪主要肢体组织在蝾螈Ambystoma mexicanum(蝾螈)肢体再生。令人惊讶的是,我们发现每个组织产生的祖细胞具有有限的潜力。因此,芽基是一个异质集合的限制祖细胞。在这些研究结果的基础上,我们进一步证明,位置的身份是一个细胞类型的特定属性的芽基细胞,其中软骨衍生的芽基细胞海港位置的身份,但施万衍生的细胞没有。我们的研究结果表明,肢体再生的复杂现象可以在不完全去分化为多能状态的情况下实现,这一结论对再生医学具有重要意义。
During limb regeneration adult tissue is converted into a zone of undifferentiated progenitors called the blastema that reforms the diverse tissues of the limb. Previous experiments have led to wide acceptance that limb tissues dedifferentiate to form pluripotent cells. Here we have reexamined this question using an integrated GFP transgene to track the major limb tissues during limb regeneration in the salamander Ambystoma mexicanum (the axolotl). Surprisingly, we find that each tissue produces progenitor cells with restricted potential. Therefore, the blastema is a heterogeneous collection of restricted progenitor cells. On the basis of these findings, we further demonstrate that positional identity is a cell-type-specific property of blastema cells, in which cartilage-derived blastema cells harbour positional identity but Schwann-derived cells do not. Our results show that the complex phenomenon of limb regeneration can be achieved without complete dedifferentiation to a pluripotent state, a conclusion with important implications for regenerative medicine.