美国霍华德休斯医学研究所Tzumin Lee和Jorge Garcia-Marques等研究人员合作取得新成果。他们提出可编程的报告子序列用于谱系分析。相关论文于2020年7月27日发表于《自然-神经科学》。

他们介绍了CLADES（由编辑序列驱动的细胞谱系访问），这是一种基于CRISPR–Cas9技术的细胞谱系研究技术。CLADES依靠基因开关系统以预定顺序激活和灭活报告基因。将CLADES靶向祖细胞可以使后代继承报道基因的顺序级联，从而将出生顺序与报道基因表达偶联。

该系统也可以通过热激在时间上诱导，使得谱系发育在时间上得以完成，因此可以通过追踪子代中表达的报道分子来解构扩展的细胞谱系。当针对种系时，相同的级联在动物世代之间进行，主要用相应的报告基因组合标记每一世代。因此，CLADES提供了一种创新的策略，可用于制作可编程级联的基因，这些基因可用于遗传操作或记录系列生物学事件。

附：英文原文

Title: A programmable sequence of reporters for lineage analysis

Author: Jorge Garcia-Marques, Isabel Espinosa-Medina, Kai-Yuan Ku, Ching-Po Yang, Minoru Koyama, Hung-Hsiang Yu, Tzumin Lee

Issue&Volume: 2020-07-27

Abstract: We present CLADES (cell lineage access driven by an edition sequence), a technology for cell lineage studies based on CRISPR–Cas9 techniques. CLADES relies on a system of genetic switches to activate and inactivate reporter genes in a predetermined order. Targeting CLADES to progenitor cells allows the progeny to inherit a sequential cascade of reporters, thereby coupling birth order to reporter expression. This system, which can also be temporally induced by heat shock, enables the temporal resolution of lineage development and can therefore be used to deconstruct an extended cell lineage by tracking the reporters expressed in the progeny. When targeted to the germ line, the same cascade progresses across animal generations, predominantly marking each generation with the corresponding combination of reporters. CLADES therefore offers an innovative strategy for making programmable cascades of genes that can be used for genetic manipulation or to record serial biological events.

DOI: 10.1038/s41593-020-0676-9

Source: https://www.nature.com/articles/s41593-020-0676-9