Engrailed-1 Potentiates Mitochondrial Transplant Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury

Spinal cord ischemia-reperfusion injury (SCI/RI) is characterized by severe mitochondrial dysfunction and neuronal apoptosis. The transcription factor Engrailed-1 (En-1) has been identified as a potential regulator of mitochondrial homeostasis and neuroprotection. In this study, we utilized an integrated multi-omics approach to elucidate the molecular mechanisms by which En-1 protects cells from ischemia-like injury. We performed RNA-sequencing (RNA-seq) on PC12 cells with stable En-1 overexpression and their respective controls under both normoxic and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. To identify direct genomic targets of En-1, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis was conducted. Integration of transcriptomic and DNA-binding profiles revealed a distinct regulatory network through which En-1 modulates mitochondrial function and cell survival. These data provide a comprehensive resource for understanding the transcriptional landscape governed by En-1 and identify potential therapeutic targets for mitigating mitochondrial damage in ischemic neural injuries.