Decoding the multidimensional signatures of resident and expanded natural killer cells generated from perinatal blood

Natural killer (NK) cells are lymphocytes and play a pivotal role in innate and adaptive immune responses against infections and malignancies. Longitudinal studies have indicated the feasibility of perinatal blood for large-scale NK cell generation, yet the systematic and detailed comparations of the signatures of resident and expanded NK cells (rNKs, eNKs) are largely obscure. Herein, we harvested rNKs from umbilical cord blood (rUC-NKs) and placental blood (rP-NKs) as well as the corresponding eNKs (eUC-NKs, eP-NKs). Furthermore, the biological properties and transcriptomic signatures including cellular subpopulations, cytotoxicity, gene expression profiling, genetic characteristics, signaling pathways and gene set-related biological process were investigated. The enriched rNKs and eNKs exhibited diversity in biomarker expression pattern, and eNKs with higher percentages of NKG2D⁺, NKG2A⁺, NKp44⁺ and NKp46⁺ subsets. rNKs or eNKs with different origins showed more similarities in transcriptomic signatures than those with the same origin. Our data revealed multifaceted similarities and differences of the indicated rNKs and pNKs both at the cellular and molecular levels. Our findings provide new references for further dissecting the efficacy and molecular mechanisms of rNKs and eNKs, which will collectively benefit the fundamental and translational studies of NK cell-based immunotherapy.