Cellular Resiliency and Survival of a Neuro-2a Cell Line Under Extreme Stress

Stressors such as hypoxia, hypothermia, and acute toxicity often result in widespread cell death. Recently, the failure of a cryostorage dewar in our lab resulted in prolonged thawing of Neuro-2a cells, exposing them to a combination of these insults. Surprisingly, a small fraction of the cells survived the event, underwent a period of near-dormancy, and were able to fully recover to a healthy state. To investigate this unusual resiliency, we established a novel standardized model to recapitulate the event and charted the phenotypes, transcriptomes, proteomes, and mitochondrial dynamics of the surviving cells along the trajectory of recovery. We observed an enrichment in DNA-repair and chromatin modification pathways bolstered by highly elevated mitochondrial activity in the immediate aftermath of the event and through the early stages of recovery, with subsequent normalization toward that of controls as the cells completed their recovery. Our results indicate that a robust energetic state that helps sustain DNA repair and stress-responsive pathways at the earliest stages of recovery facilitate cell survival and resiliency following extreme stress.