Nkx6.1 plays an essential role during the embryonic development of the spinal cord. However, its role in the adult and injured spinal cord is not well understood. Here we show that lentivirus-mediated Nkx6.1 expression in the adult injured mouse spinal cord promotes cell proliferation and activation of endogenous neural stem/progenitor cells (NSPCs) at the acute phase of injury. In the chronic phase, Nkx6.1 increases the number of interneurons, reduces the number of reactive astrocytes, minimizes glial scar formation, and represses neuroinflammation. Transcriptomic analysis reveals that Nkx6.1 upregulates the sequential expression of genes involved in cell proliferation, neural differentiation, and Notch signaling pathway, downregulates genes and pathways involved in neuroinflammation, reactive astrocyte activation, and glial scar formation. Together, our findings support the potential role of Nkx6.1 in neural regeneration in the adult injured spinal cord.

Nkx6.1 在脊髓胚胎发育过程中起着至关重要的作用。然而，它在成人和受伤脊髓中的作用尚不清楚。在这里，我们显示慢病毒介导的 Nkx6.1 在成年受伤小鼠脊髓中的表达促进了损伤急性期内源性神经干/祖细胞 (NSPCs) 的细胞增殖和活化。在慢性期，Nkx6.1 增加中间神经元的数量，减少反应性星形胶质细胞的数量，最大限度地减少胶质瘢痕形成，并抑制神经炎症。转录组学分析表明，Nkx6.1 上调参与细胞增殖、神经分化和 Notch 信号通路的基因的顺序表达，下调参与神经炎症、反应性星形胶质细胞活化和胶质瘢痕形成的基因和通路。