Uncovering the developmental trajectory of Natural Killer cells

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Objectives- Identify and characterize Natural Killer (NK) cell progenitors and intermediate cell subsets that transition from CD34+ progenitors to terminal NK cell populations.- Determine the transcriptional regulatory networks (transcriptional factors and pathways)that govern the differentiation process of CD34+ progenitors into NK cells.- Determine the biological pathways and networks that give rise to the higher proportion of cytotoxic NK cells when incubated with pre-differentiation media.- Utilize the gene signatures of NK progenitors and intermediate cell populations to analyze public datasets to identify sites and contexts in the body where NK cell differentiation occurs.We aim to use trajectory analysis to map the differentiation of NK cells from CD34+ progenitors and employ tradeSeq to pinpoint genes differentially expressed across these trajectories. Additionally, SCENIC will be used to reveal the transcriptional networks governing NK cell differentiation. The findings, including gene signatures of NKPs and early differentiation subsets, will be applied to public single-cell datasets of bone marrow and lymphoid organs to ascertain the primary sites of NK cell differentiation and to guide future research efforts.