Analyzing dendritic cell development by inducible lineage tracing

通过诱导谱系追踪分析树突状细胞发育

• 批准号: 9101974
• 负责人: Boris Reizis
• 金额: $ 21.19万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9101974
• 关键词: Adoptive Transfer; Adult; Antigens; Bone Marrow; Cells; Dendritic Cells; Dependence; Development; Gene Targeting; Genes; Genetic Recombination; Health; Hematopoietic stem cells; Immune; Immune response; Interferon Type I; Interferons; Kinetics; Label; Ligands; Link; Modeling; Molecular; Molecular Profiling; Mouse Strains; Mus; Organism; Population; Property; Reporter; Sentinel; Tamoxifen; Transgenic Mice; Transplantation; Update; Vaccine Design; Work; adaptive immunity; base; cell type; cytokine; in vivo; novel; pathogen; progenitor; recombinase; stem; stem cell differentiation

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.

描述（由申请人提供）：树突状细胞（DC）是关键的免疫前哨，将病原体的先天识别与适应性免疫反应联系起来。 DC包括两个主要的进化保守亚集，即I型干扰素产生浆细胞样DC（PDC）和抗原呈递经典DCS（CDC）。两个DC子集对细胞因子FLT3配体具有共同的依赖性，但它们的细胞和分子特性非常不同。目前，人们认为CDC和PDC是由骨髓中常见的DC祖细胞（CDP）发展出来的。但是，最近的一些证据与该模型不兼容，可以使用体内谱系跟踪对DC开发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（CRER）的转基因小鼠菌株来标记茎/祖先群体并将其分化为DC。具体来说，我们将检查 造血干细胞分化为DC子集的动力学和序列（AIM 1）和CDPS的分化潜力（AIM 2）。这些研究将基于体内谱系跟踪产生DC开发的更新模型。他们还将产生新的菌株，以诱导CRE重组，并用实用性来进行谱系跟踪和基因靶向。