biostudies-literatureKim HJNational Institute of Neurological Disorders and StrokeNEI NIH HHSNational Eye InstituteRRD VANINDS NIH HHSNational Institutes of HealthU.S. Department of Veterans AffairsNational Institute of General Medical SciencesCraig H. Neilsen FoundationNIH HHSNIGMS NIH HHS3953-3969.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC10843387biostudies-literatureUnknown111(24)Despite substantial progress in understanding the biology of axon regeneration in the CNS, our ability to promote regeneration of the clinically important corticospinal tract (CST) after spinal cord injury remains limited. To understand regenerative heterogeneity, we conducted patch-based single-cell RNA sequencing on rare regenerating CST neurons at high depth following PTEN and SOCS3 deletion. Supervised classification with Garnett gave rise to a Regeneration Classifier, which can be broadly applied to predict the regenerative potential of diverse neuronal types across developmental stages or after injury. Network analyses highlighted the importance of antioxidant response and mitochondrial biogenesis. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator ofNeuronDeep scRNA sequencing reveals a broadly applicable Regeneration Classifier and implicates antioxidant response in corticospinal axon regeneration.PMC10843387648861RX002483R01 NS054734GM145427T32 GM008666NS093055P30 EY012196P30 NS047101R01 NS093055I01 RX002483S10 OD026929T32 GM145427GM008666733544EY012196Saikia JMSanchez JJLi HZhang JKim HJLusk DTMonte KMAAgba CKHernaiz-Llorens MChavez-Martinez CLZheng BMoore AXHa ERomaus-Sanjurjo DCervantes KMfalseDeep scRNA sequencing reveals a broadly applicable Regeneration Classifier and implicates antioxidant response in corticospinal axon regeneration.Despite substantial progress in understanding the biology of axon regeneration in the CNS, our ability to promote regeneration of the clinically important corticospinal tract (CST) after spinal cord injury remains limited. To understand regenerative heterogeneity, we conducted patch-based single-cell RNA sequencing on rare regenerating CST neurons at high depth following PTEN and SOCS3 deletion. Supervised classification with Garnett gave rise to a Regeneration Classifier, which can be broadly applied to predict the regenerative potential of diverse neuronal types across developmental stages or after injury. Network analyses highlighted the importance of antioxidant response and mitochondrial biogenesis. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator of2023-01-01T00:00:00Z2023 Dec2026-06-01T19:49:21.718Z2025-04-04T00:39:02.914ZS-EPMC108433873784802410.1016/j.neuron.2023.09.019