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Deciphering neural heterogeneity through cell lineage tracing
Cellular and Molecular Life Sciences ( IF 8 ) Pub Date : 2020-11-05 , DOI: 10.1007/s00018-020-03689-3
María Figueres-Oñate , Rebeca Sánchez-González , Laura López-Mascaraque

Understanding how an adult brain reaches an appropriate size and cell composition from a pool of progenitors that proliferates and differentiates is a key question in Developmental Neurobiology. Not only the control of final size but also, the proper arrangement of cells of different embryonic origins is fundamental in this process. Each neural progenitor has to produce a precise number of sibling cells that establish clones, and all these clones will come together to form the functional adult nervous system. Lineage cell tracing is a complex and challenging process that aims to reconstruct the offspring that arise from a single progenitor cell. This tracing can be achieved through strategies based on genetically modified organisms, using either genetic tracers, transfected viral vectors or DNA constructs, and even single-cell sequencing. Combining different reporter proteins and the use of transgenic mice revolutionized clonal analysis more than a decade ago and now, the availability of novel genome editing tools and single-cell sequencing techniques has vastly improved the capacity of lineage tracing to decipher progenitor potential. This review brings together the strategies used to study cell lineages in the brain and the role they have played in our understanding of the functional clonal relationships among neural cells. In addition, future perspectives regarding the study of cell heterogeneity and the ontogeny of different cell lineages will also be addressed.



中文翻译:

通过细胞谱系追踪了解神经异质性

从成年的增殖和分化祖细胞中了解成年大脑如何达到合适的大小和细胞组成是发育神经生物学中的一个关键问题。在这个过程中,不仅要控制最终大小,而且要正确安排不同胚胎来源的细胞的排列。每个神经祖细胞必须产生精确数量的同胞来建立克隆,所有这些克隆将聚集在一起形成功能性的成年神经系统。谱系细胞追踪是一个复杂且具有挑战性的过程,旨在重建单个祖细胞产生的后代。可以通过基于遗传修饰生物的策略(使用遗传示踪剂,转染的病毒载体或DNA构建体,甚至单细胞测序)来实现此跟踪。十多年来,结合不同的报道蛋白和转基因小鼠的使用,彻底改变了克隆分析方法。如今,新型基因组编辑工具和单细胞测序技术的可用性极大地提高了谱系追踪能力以破译祖细胞。这篇综述汇集了用于研究脑细胞谱系的策略及其在我们对神经细胞之间功能性克隆关系的理解中所扮演的角色。另外,还将探讨有关细胞异质性和不同细胞谱系的个体发育研究的未来观点。新型基因组编辑工具和单细胞测序技术的可用性极大地提高了谱系追踪能力以破译祖细胞潜能。这篇综述汇集了用于研究脑细胞谱系的策略及其在我们对神经细胞之间功能性克隆关系的理解中所扮演的角色。另外,还将探讨有关细胞异质性和不同细胞谱系的个体发育研究的未来观点。新型基因组编辑工具和单细胞测序技术的可用性极大地提高了谱系追踪能力以破译祖细胞潜能。这篇综述汇集了用于研究脑细胞谱系的策略及其在我们对神经细胞之间功能性克隆关系的理解中所扮演的角色。另外,还将探讨有关细胞异质性和不同细胞谱系的个体发育研究的未来观点。

更新日期:2020-11-05
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