近日，中山大学 Xionglei He 和 Li Liu 共同合作取得了重要工作进展，他们绘制单细胞分辨率细胞系统发育图，揭示器官发育过程中的细胞群动态。相关论文于2021年12月2日在线发表于《自然—方法学》杂志上。

在这里，科研人员开发了一种替代突变辅助的谱系追踪系统（substitution mutation-aided lineage-tracing system, SMALT），在绘制细胞系统发育图方面优于现有的细胞条形码方法。他们将SMALT应用于黑腹果蝇（Drosophila melanogaster），在早期成年细胞中平均每 3000 个碱基对序列就能获得 20 多个突变。利用条形码突变，研究人员获得了高质量的细胞系统发育进化树，每个都包含数千个具有 84-93% 中值引导支持的内部节点。

获得的细胞系统发育图能够进行群体遗传分析，能够预测在发育过程中每个器官亲代细胞活跃分裂的次数（the number of actively dividing parental cells, Np）的纵向动态。Np 动态揭示了细胞发育的轨迹，并为对称和非对称细胞分裂的平衡提供了见解。

据了解，绘制复杂的多细胞生物细胞系统发育图，依赖于从受精卵发育到成体过程中所积累的体细胞突变。现有的细胞条形码方法，每个条形码大约可以记录3个突变，只能实现绘制复杂生物细胞系统的低分辨率发育图。

附：英文原文

Title: Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development

Author: Liu, Kehui, Deng, Shanjun, Ye, Chang, Yao, Zeqi, Wang, Jianguo, Gong, Han, Liu, Li, He, Xionglei

Issue&Volume: 2021-12-02

Abstract: Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average more than 20 mutations on a three-kilobase-pair barcoding sequence in early-adult cells. Using the barcoding mutations, we obtained high-quality cell phylogenetic trees, each comprising several thousand internal nodes with 84–93% median bootstrap support. The obtained cell phylogenies enabled a population genetic analysis that estimates the longitudinal dynamics of the number of actively dividing parental cells (Np) in each organ through development. The Np dynamics revealed the trajectory of cell births and provided insight into the balance of symmetric and asymmetric cell division.

DOI: 10.1038/s41592-021-01325-x

Source: https://www.nature.com/articles/s41592-021-01325-x