Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, and Department of Developmental Biology,
Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, and
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9846-51. doi: 10.1073/pnas.1410097111. Epub 2014 Jun 23.
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.
周围神经系统对哺乳动物附肢组织替代的需求和影响在很大程度上仍未得到明确界定。为了探索这个问题，我们对在趾尖再生、正常维持和皮肤伤口愈合过程中，没有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。我们表明，细胞更替、替代和细胞分化，来自后肢组织中假定的组织干细胞/祖细胞，在很大程度上独立于神经和神经衍生的因素保持完整。然而，没有神经的再生趾尖在骨骼和指甲基质中显示出形态缺陷。这些依赖神经的表型类似于因脊髓损伤而导致神经损伤的患者的临床观察，对于旨在了解神经对人类损伤病因影响的转化医学具有重要意义。
