GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318453/primaryOK200Methylation profilingHomo sapiensMethylation profiling by genome tiling arrayhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318453GEOGSEfalseIL-15 Signaling During a Critical NK Cell Developmental Window Subverts Maturation and KIR Acquisition [Methylation array]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.2026/08/21GSE318453GSM9495183GSM9495184GSM9495140GSM9495141GSM9495185GSM9495186GSM9495142GSM9495180GSM9495181GSM9495182GSM9495147GSM9495148GSM9495149GSM9495187GSM9495143GSM9495144GSM9495188GSM9495189GSM9495145GSM9495146GSM9495194GSM9495150GSM9495195GSM9495151GSM9495152GSM9495196GSM9495197GSM9495153GSM9495190GSM9495191GSM9495192GSM9495193GSM9495158GSM9495159GSM9495198GSM9495154GSM9495155GSM9495199GSM9495156GSM9495157GSM9495161GSM9495162GSM9495163GSM9495164GSM9495160GSM9495169GSM9495165GSM9495166GSM9495167GSM9495168GSM9495172GSM9495173GSM9495174GSM9495175GSM9495170GSM9495171GSM9495136GSM9495137GSM9495138GSM9495139GSM9495176GSM9495177GSM9495178GSM9495134GSM9495135GSM94951792114533022318453Homo sapiens