Analyzing dendritic cell development by inducible lineage tracing

描述（由申请人提供）：树突状细胞（dc）是连接病原体先天识别和适应性免疫反应的关键免疫哨兵。dc包括两个主要的进化上保守的亚群，I型干扰素产生浆细胞样dc （pDCs）和抗原呈递经典dc （cdc）。这两个DC亚群对细胞因子Flt3配体有共同的依赖性，但它们的细胞和分子特性非常不同。目前认为，cdc和pDCs由骨髓中共同的DC祖细胞（CDP）发展而来。然而，最近的一些证据与该模型不兼容，因此需要使用体内谱系追踪技术对DC的发展进行公正的重新检查。我们将使用表达他莫昔芬诱导的Cre重组酶（CreER）的转基因小鼠菌株来标记干/祖群体，并追踪它们向dc的分化。具体来说，我们将检查

DESCRIPTION (provided by applicant): Dendritic cells (DCs) are key immune sentinels that link innate recognition of pathogens to adaptive immune responses. DCs comprise two main evolutionarily conserved subsets, type I interferon- producing plasmacytoid DCs (pDCs) and antigen-presenting classical DCs (cDCs). The two DC subsets share common dependence on the cytokine Flt3 ligand, yet their cellular and molecular properties are very distinct. It is currently believed that cDCs and pDCs develop from a common DC progenitor (CDP) in the bone marrow. However, some recent evidence is not compatible with this model, warranting an unbiased re-examination of DC development using lineage tracing in vivo. We will use transgenic mouse strains expressing a tamoxifen-inducible Cre recombinase (CreER) to label stem/progenitor populations and trace their differentiation into DCs. Specifically, we will examine the kinetics and sequence of hematopoietic stem cell differentiation into DC subsets (Aim 1) and the differentiation potential of CDPs (Aim 2). These studies would generate an updated model of DC development based on in vivo lineage tracing. They would also generate novel strains for inducible Cre recombination with utility for lineage tracing and gene targeting.