Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1A8, Canada.
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
Cell Stem Cell. 2019 Feb 7;24(2):240-256.e9. doi: 10.1016/j.stem.2018.10.024. Epub 2018 Nov 29.
Peripheral innervation plays an important role in regulating tissue repair and regeneration. Here we provide evidence that injured peripheral nerves provide a reservoir of mesenchymal precursor cells that can directly contribute to murine digit tip regeneration and skin repair. In particular, using single-cell RNA sequencing and lineage tracing, we identify transcriptionally distinct mesenchymal cell populations within the control and injured adult nerve, including neural crest-derived cells in the endoneurium with characteristics of mesenchymal precursor cells. Culture and transplantation studies show that these nerve-derived mesenchymal cells have the potential to differentiate into non-nerve lineages. Moreover, following digit tip amputation, neural crest-derived nerve mesenchymal cells contribute to the regenerative blastema and, ultimately, to the regenerated bone. Similarly, neural crest-derived nerve mesenchymal cells contribute to the dermis during skin wound healing. These findings support a model where peripheral nerves directly contribute mesenchymal precursor cells to promote repair and regeneration of injured mammalian tissues.
周围神经支配在调节组织修复和再生中起着重要作用。在这里，我们提供的证据表明，受伤的周围神经提供了间充质前体细胞的储备库，这些细胞可以直接有助于小鼠指尖再生和皮肤修复。特别是，我们通过单细胞 RNA 测序和谱系追踪，在对照和受伤的成年神经中鉴定出转录上不同的间充质细胞群体，包括具有间充质前体细胞特征的神经内膜中的神经嵴衍生细胞。培养和移植研究表明，这些神经来源的间充质细胞具有分化为非神经谱系的潜力。此外，在指尖截断后，神经嵴衍生的神经间充质细胞有助于再生性胚基的形成，最终有助于再生骨的形成。类似地，神经嵴衍生的神经间充质细胞在皮肤伤口愈合过程中有助于真皮的形成。这些发现支持这样一种模型，即周围神经直接提供间充质前体细胞，以促进受伤的哺乳动物组织的修复和再生。
