Uncovering the developmental trajectory of Natural Killer cells

目的-鉴定和表征自然杀伤（NK）细胞祖细胞和从CD 34+祖细胞转变为终末NK细胞群体的中间细胞亚群。确定控制CD 34+祖细胞分化为NK细胞过程的转录调控网络（转录因子和途径）。确定与预分化培养基孵育时产生较高比例的细胞毒性NK细胞的生物学途径和网络。利用NK祖细胞和中间细胞群体的基因特征来分析公共数据集，以确定NK细胞分化发生的部位和背景。我们的目标是使用轨迹分析来绘制NK细胞从CD 34+祖细胞分化的图谱，并使用tradeSeq来确定在这些轨迹中差异表达的基因。此外，SCENIC将用于揭示控制NK细胞分化的转录网络。这些发现，包括NKPs和早期分化亚群的基因特征，将应用于骨髓和淋巴器官的公共单细胞数据集，以确定NK细胞分化的主要位点，并指导未来的研究工作。

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.