Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration
Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration
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DOI：
10.1073/pnas.1410097111
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发表时间：
2014-07-08
影响因子：
11.1
通讯作者：
Longaker, Michael T.
中科院分区：
文献类型：
--
作者：
Rinkevich, Yuval;Montoro, Daniel T.;Longaker, Michael T.
周围神经系统对哺乳动物附属物组织替代的要求和影响在很大程度上仍未明确。为了探讨这个问题，我们对指尖再生、正常维持和皮肤伤口愈合过程中缺乏神经供应的小鼠后肢组织的单个细胞进行了遗传谱系追踪和克隆分析。我们发现，后肢组织中来自组织干细胞/祖细胞的细胞更新、替换和细胞分化在很大程度上保持完整，不受神经和神经源性因素的影响。然而，在没有神经的情况下，再生的指尖在骨和甲基质中显示出图案缺陷。这些神经依赖性表型模拟了脊髓损伤引起的神经损伤患者的临床观察结果，对于旨在了解神经对人体损伤病因的影响的转化医学具有重要意义。
The requirement and influence of the peripheral nervous system on tissue replacement in mammalian appendages remain largely undefined. To explore this question, we have performed genetic lineage tracing and clonal analysis of individual cells of mouse hind limb tissues devoid of nerve supply during regeneration of the digit tip, normal maintenance, and cutaneous wound healing. We show that cellular turnover, replacement, and cellular differentiation from presumed tissue stem/progenitor cells within hind limb tissues remain largely intact independent of nerve and nerve-derived factors. However, regenerated digit tips in the absence of nerves displayed patterning defects in bone and nail matrix. These nerve-dependent phenotypes mimic clinical observations of patients with nerve damage resulting from spinal cord injury and are of significant interest for translational medicine aimed at understanding the effects of nerves on etiologies of human injury.