Multicellular development depends on the differentiation of cells into specific fates with precise spatial organization. Lineage history plays a pivotal role in cell fate decisions, but is inaccessible in most contexts. Engineering cells to actively record lineage information in a format readable in situ would provide a spatially resolved view of lineage in diverse developmental processes. Here, we introduce a serine integrase-based recording system that allows in situ readout, and demonstrate its ability to reconstruct lineage relationships in cultured stem cells and flies. The system, termed intMEMOIR, employs an array of independent three-state genetic memory elements that can recombine stochastically and irreversibly, allowing up to 59,049 distinct digital states. intMEMOIR accurately 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 clonal analysis and recording in diverse systems.

中文翻译：

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用合成数字记录系统对细胞谱系进行成像

多细胞发育取决于具有精确空间组织的细胞分化为特定命运的能力。沿袭历史在细胞命运决定中起着举足轻重的作用，但在大多数情况下是不可访问的。工程单元以现场可读的格式主动记录沿袭信息会在不同的开发过程中提供沿袭的空间解析视图。在这里，我们介绍了一种基于丝氨酸整合酶的记录系统，该系统可以原位读出，并证明其在培养的干细胞和果蝇中重建谱系关系的能力。该系统称为intMEMOIR，它采用了一系列独立的三态遗传记忆元件，可以随机且不可逆地重组，从而允许多达59,049个不同的数字态。intMEMOIR可以准确地重建干细胞中的谱系树，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。这些结果为在各种系统中显微镜可读的克隆分析和记录奠定了基础。