美国加州理工学院Michael B. Elowitz和Carlos Lois小组在研究中取得进展。他们利用合成数字记录系统对细胞谱系进行成像。该项研究成果发表在2021年4月9日出版的《科学》上。

使用基于丝氨酸整合酶的记录系统，研究人员对细胞进行了改造以原位读取的方式记录谱系信息。研究人员将这套系统命名为整合酶可编辑内存，其通过工程诱变和光学原位读取（intMEMOIR）可在培养的小鼠细胞和果蝇中进行谱系关系的原位重建。

intMEMOIR使用一系列独立的三态遗传记忆元件，可随机、不可逆地重塑，从而可运行超过59,049个不同的数字态。其在干细胞中重建了谱系树，并能够同时分析果蝇大脑切片中的单细胞克隆历史、空间位置和基因表达。这些结果为各种系统中显微镜可读谱系记录和分析奠定了基础。

据悉，在多细胞发育过程中，空间位置和谱系来源在控制细胞命运决定中起着重要作用。

附：英文原文

Title: Imaging cell lineage with a synthetic digital recording system

Author: Ke-Huan K. Chow, Mark W. Budde, Alejandro A. Granados, Maria Cabrera, Shinae Yoon, Soomin Cho, Ting-hao Huang, Noushin Koulena, Kirsten L. Frieda, Long Cai, Carlos Lois, Michael B. Elowitz

Issue&Volume: 2021/04/09

Abstract: During multicellular development, spatial position and lineage history play powerful roles in controlling cell fate decisions. Using a serine integrase–based recording system, we engineered cells to record lineage information in a format that can be read out in situ. The system, termed integrase-editable memory by engineered mutagenesis with optical in situ readout (intMEMOIR), allowed in situ reconstruction of lineage relationships in cultured mouse cells and flies. intMEMOIR uses an array of independent three-state genetic memory elements that can recombine stochastically and irreversibly, allowing up to 59,049 distinct digital states. It reconstructed lineage trees in stem cells and enabled simultaneous analysis of single-cell clonal history, spatial position, and gene expression in Drosophila brain sections. These results establish a foundation for microscopy-readable lineage recording and analysis in diverse systems.

DOI: 10.1126/science.abb3099

Source: https://science.sciencemag.org/content/372/6538/eabb3099