Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip.

Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip.
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DOI:
10.1038/nature10346
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发表时间:
2011-08-24
期刊:
影响因子:
64.8
通讯作者:
Weissman, Irving L.
Weissman, Irving L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Rinkevich, Yuval;Lindau, Paul;Ueno, Hiroo;Longaker, Michael T.;Weissman, Irving L.

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截肢和手指远端的再生代表了两栖动物、鱼类和小鼠的组织再生模型。几十年来,人们一直认为肢体再生源自胚基,胚基是一种未分化的多能细胞群,被认为是通过去分化从成熟细胞衍生而来。在这里,我们展示了多种组织干/祖细胞有助于恢复小鼠远端手指。对单个细胞的遗传命运图谱和克隆分析表明,这些干细胞是谱系受限的,模仿发育过程中的手指生长。表达 CFP 的造血干细胞的移植,以及基因标记小鼠之间的共生,证实了干细胞/祖细胞是组织驻留的,包括参与血管生成的细胞。这些结果与低等脊椎动物的附肢发育/再生的结果相结合,共同证明组织干细胞而不是多能胚细胞是截肢后肢体再生的进化保守的细胞模式。
The regrowth of amputated limbs and the distal tips of digits represent models of tissue regeneration in amphibians, fish, and mice. For decades it had been assumed that limb regeneration derived from the blastema, an undifferentiated pluripotent cell population thought to be derived from mature cells via dedifferentiation. Here we show that a wide-range of tissue stem/progenitor cells contribute to restore the mouse distal digit. Genetic fate mapping and clonal analysis of individual cells revealed that these stem cells are lineage restricted, mimicking digit growth during development. Transplantation of CFP expressing hematopoietic stem cells, and parabiosis between genetically marked mice, confirmed that the stem/progenitors are tissue resident, including the cells involved in angiogenesis. These results, combined with those from appendage development/regeneration in lower vertebrates, collectively demonstrate that tissue stem cells rather than pluripotent blastema cells are an evolutionarily conserved cellular mode for limb regeneration after amputation.
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