Unravelling the clonal nature of microglial diversity in the brain

技能优先顺序：定量生物学小胶质细胞是大脑中驻留的巨噬细胞，在大脑发育和功能、健康和疾病方面发挥着关键作用。小胶质细胞是从卵黄囊发育而来的，卵黄囊是与大多数其他组织驻留的巨噬细胞不同的起源和谱系。在少数祖细胞在大脑中定居后，种群经历了大规模的扩张，在出生后不久就达到了成年的密度。这一过程表明，具有潜在不同特性的细胞亚群数量有限。在这个项目中，我们将使用一个尖端的工具箱，通过多色转基因和病毒方法标记和绘制卵黄囊来源细胞的命运图，并使用定制的微流控技术在单细胞水平上分析转录图谱。这种设置将允许研究我们的假设：小胶质细胞群体由有限数量的亚群组成，由发育决定，定义了区域和功能的异质性。对小胶质细胞群体组成的洞察将有助于了解这些细胞在健康和患病大脑中的作用，特别是与年龄相关的神经疾病的作用。

Skills Priority Alignment: Quantitative BiologyMicroglia, the brain's resident macrophages, have key roles in brain development and function, in health and disease. Microglia are developmentally derived from the yolk sac, a distinct origin and lineage from the majority of other tissue-resident macrophages. After a few progenitors colonize the brain, the population undergoes massive expansion, achieving the adult density shortly after birth. This process suggests the generation of a limited number of subpopulations of cells with potentially diverse properties. In this project we will use a cutting-edge toolbox to label and fate-map yolk sac derived cells with multicolour transgenic and viral approaches, combined with the analysis of the transcriptional profile at the single-cell level, using bespoke microfluiding technologies. This setup will allow the study of our hypothesis: the microglial population is composed by a limited number of subpopulations, dictated from development, defining regional and functional heterogeneity. Insights into the composition of the microglial population will inform on the roles of these cells in the healthy and diseased brain, with particular relevance for age-related neurological disorders.