Nkx6.1 enhances neural stem cell activation and attenuates glial scar formation and neuroinflammation in the adult injured spinal cord

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.

Automated summary

Nkx6.1 expression in the adult injured spinal cord promotes cell proliferation and activation of endogenous neural stem/progenitor cells, leading to increased interneuron number, reduced reactive astrocytes, minimized glial scar formation, and repressed neuroinflammation. Transcriptomic analysis reveals upregulation of genes involved in cell proliferation, neural differentiation, and Notch signaling pathway, as well as downregulation of genes and pathways related to neuroinflammation, astrocyte activation, and glial scar formation. It supports the potential role of Nkx6.1 in neural regeneration in the adult injured spinal cord.