Ambient oxygen disrupts amino acid homeostasis and impairs human hematopoietic stem and progenitor cell engraftment.

Ambient oxygen exposure during ex vivo handling rapidly disrupts amino acid homeostasis and impairs human hematopoietic stem and progenitor cell engraftment.

• Why it matters: Hematopoietic stem cell transplantation is limited by cell loss and reduced stem-cell fitness, which may be worsened by routine oxygen exposure outside the hypoxic marrow niche, potentially affecting transplant success.
• What they did: The study used quantitative LC-MS profiling and single-cell analyses on human CD34+ cells to compare the effects of ambient oxygen versus hypoxia, focusing on amino acid levels, nutrient-sensing pathways, and engraftment outcomes, including interventions like amino acid restriction and LAT1 inhibition.
• The result: Ambient oxygen exposure increased intracellular amino acids and mTORC1 signaling, impairing engraftment, but transient amino acid restriction or LAT1 inhibition restored lysosomal programs and improved human HSPC engraftment.