Ali Ishaq, “Single-Cell Transcriptomes of NK Cells Responding to MCMV Infection Reveal a Distinct Ly49HHi Memory Subset Emerging 7 Days Post-infection”
Mentor: Subramaniam Malarkannan, MCW Cancer Center
Poster #87

Natural Killer (NK) cells play a crucial role in the early management and clearance of mouse cytomegalovirus (MCMV) infection. CMV infection is one of the most common post-transplant complications and a significant determinant of morbidity and mortality following allogeneic hematopoietic stem cell transplantation, which is the major therapeutic approach for hematological malignancies. In murine models, Ly49H+ NK cells can specifically recognize and eliminate infected cells presenting the murine CMV (MCMV) m157 glycoprotein. Following activation, Ly49H+ NK cells undergo expansion and form a reservoir of adaptive-like cells that exhibit enhanced capabilities of targeting future infections. The molecular mechanism by which adaptive NK cells develop and their transcriptomic profiles have not been fully defined. Here we infected C57BL/B6 mice at different time points with MCMV and performed single-cell RNA-sequencing (scRNA-seq) on NK cells isolated from the spleen. Unsupervised clustering revealed a distinct adaptive-like Ly49HHi subset that was found at elevated levels 7 days post-infection. This Ly49HHi subset had high expression of Cd3e, Cd3d, CD74, Emb, Batf3, and Ltb. Our developmental trajectory analysis of adaptive Ly49H+ NK cells revealed a unique branchpoint leading to the development of memory NK. These findings enhance our understanding of memory NK cells and have the potential to influence their future therapeutic applications.