中山大学Xionglei He研究组通过胚胎发育过程中的连续条形码突变实现斑马鱼单细胞分辨率谱系追踪。相关论文于2024年4月15日在线发表在《遗传学报》上。

研究人员在斑马鱼中实施了SMALT系统，记录了受精后一天胚胎的一千位碱基对条形码序列上14个替换突变的中位数。利用该系统，研究人员重建了斑马鱼鳍细胞的四种细胞谱系树，包括原始鳍和再生鳍。每棵树都由数百个内部节点组成，中位引导支持率为99%。

对获得细胞谱系树的分析表明，再生鳍细胞主要来源于鳍同一部位的细胞。通过对同一个体的生殖细胞进行多次取样，研究人员证实了生殖细胞池的稳定性以及生殖细胞和体细胞祖细胞的早期分离。该系统为重建不同组织的高质量细胞系统发育提供了可能，也为斑马鱼的发育和疾病提供了宝贵的见解。

据了解，要加深人们对发育生物学和干细胞生物学的理解，就必须弄清来自一个合子的所有后代的谱系关系。然而，斑马鱼现有的细胞条形码技术缺乏分辨率，无法捕捉胚胎发生过程中的大部分细胞分裂。最近开发的一种方法SMALT成功地重建了黑腹果蝇的高分辨率细胞系统发生树。

附：英文原文

Title: Achieving single-cell-resolution lineage tracing in zebrafish by continuous barcoding mutations during embryogenesis

Author: Xionglei He

Issue&Volume: 2024/04/15

Abstract: Unraveling the lineage relationships of all descendants from a zygote is fundamental to advancing our understanding of developmental and stem cell biology. However, existing cell barcoding technologies in zebrafish lack the resolution to capture the majority of cell divisions during embryogenesis. A recently developed method, SMALT, successfully reconstructed high-resolution cell phylogenetic trees for Drosophila melanogaster. Here, we implement the SMALT system in zebrafish, recording a median of 14 substitution mutations on a one-kilobase-pair barcoding sequence for one-day post-fertilization embryos. Leveraging this system, we reconstruct four cell lineage trees for zebrafish fin cells, encompassing both original and regenerated fin. Each tree consists of hundreds of internal nodes with a median bootstrap support of 99%. Analysis of the obtained cell lineage trees reveals that regenerated fin cells mainly originate from cells in the same part of the fins. Through multiple times sampling germ cells from the same individual, we confirm the stability of the germ cell pool and the early separation of germ cell and somatic cell progenitors. Our system offers the potential for reconstructing high-quality cell phylogenies across diverse tissues, providing valuable insights into development and disease in zebrafish.

DOI: 10.1016/j.jgg.2024.04.004

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724000742