Uncovering the developmental trajectory of Natural Killer cells

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.