Neutral Sphingomyelinase Blockade Enhances Hematopoietic Stem Cell Fitness Through an Integrated Stress Response

Researchers demonstrated that pharmacologic and genetic inhibition of neutral sphingomyelinase-2 leads to sustained improvements in long-term competitive transplantation efficiency after ex vivo culture. Mechanistically, nSMase2 blockade activated a canonical integrated stress response and promoted metabolic quiescence in human and murine HSPCs.