程序性细胞死亡基因11（PDCD11）在斑马鱼胚胎组织特异性巨噬细胞发育中生物学作用的研究

组织驻留巨噬细胞对调控组织稳态及器官炎症反应均有重要作用。组织驻留巨噬细胞无论在分子调控还是生物学功能上，都与成年骨髓来源的巨噬细胞不同。我们的预初研究发现在斑马鱼胚胎发育过程中，细胞程序性死亡蛋白 (PDCD11)基因的缺失特异性地导致小胶质细胞祖细胞csf1r阳性的巨噬细胞减少，提示pdcd11可能参与促进早期组织驻留巨噬细胞的分化。因此，本课题将利用CRISP9介导的基因knockout技术，反义寡核苷酸链（morpholino，MO）介导的knockdown技术，分子生物学和细胞生物学技术，以及构建不同的转基因鱼系等方法，深入研究PDCD11对组织驻留巨噬细胞发育及功能的影响。明确组织驻留巨噬细胞的起源及分子调控路径将有助于我们深入了解其在不同疾病中的作用，并促进寻找新的巨噬细胞靶向治疗方案。

Tissue resident macrophages play pivotal roles in tissue homeostasis and organ inflammation. During recent years, the new paradigm has suggested the distinct origin and regulatory mechanisms of tissue resident macrophages distinguish them from bone marrow (BM) originated macrophages. Our preliminary data has identified loss of programmed cell death protein (pdcd11), a novel protein, resulted in specific abnormalities of csf1r positive tissue resident macrophage progenitors . Here we will use model organism zebrafish, in combination with a variety of experimental methods including CRISPR/Cas9 mediated gene knockout technology, MO-mediated gene knock down technology, and establishment of different transgenic zebrafish lines, to study the role of pdcd11 in tissue resident macrophage development. Defining the origins and developmental pathways of tissue-resident macrophages should help refine our understanding of the role of these cells in various disease settings and enable the design of novel macrophage-targeted therapies.