GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318529/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318529GEOGSEfalseIL-15 Signaling During a Critical NK Cell Developmental Window Subverts Maturation and KIR Acquisition [RNA-Seq]Natural killer (NK) cells are key mediators of immune surveillance following hematopoietic stem cell transplantation (HSCT). However, despite the known post-conditioning spike in interleukin-15 (IL-15), NK cell maturation is frequently delayed following HSCT. We found that during in vitro NK cell development from CD34+ hematopoietic progenitor cells (HPCs), early exposure to IL-15 drove aberrant mTOR activation, resulting in epigenetic and transcriptional dysregulation and suppressed maturation and KIR acquisition. In contrast, transiently withholding IL-15 or blocking mTOR with rapamycin produced NK cell developmental intermediates intrinsically poised to mature into highly functional, KIR-expressing NK cells. Single-cell analysis of HSCT patients at early time points post-transplant revealed a similar aberrant transcriptional signature of IL-15/mTOR overactivation in circulating donor-derived NK cells. These findings define a developmental window during which IL-15 signaling can paradoxically subvert NK cell maturation and KIR acquisition, suggesting that temporally regulated cytokine signaling could accelerate immune reconstitution and improve therapeutic efficacy.2026/08/21GSE318529GSM9497164GSM9497163GSM9497166GSM9497165GSM9497160GSM9497171GSM9497170GSM9497173GSM9497162GSM9497161GSM9497172GSM9497168GSM9497157GSM9497156GSM9497167GSM9497159GSM9497158GSM949716934284318529Homo sapiens