近日，澳大利亚墨尔本大学教授Shalin H. Naik及其研究团队探明了LoxCode体内条形码显示外胚层克隆对胎儿器官的命运偏向。相关论文于2025年5月15日发表于国际顶尖学术期刊《细胞》杂志上。

研究组开发了高多样性的Cre重组酶驱动的LoxCode条形码，用于大量组织和单细胞读数的体内克隆谱系追踪。胚胎日(E) 5.5前原肠胚在子宫内进行条形码，并评估外胚层克隆对E12.5胚胎广泛组织的贡献。一些外胚层克隆在胚层上有广泛的贡献，而许多外胚层、间充质或肢体在组织区室和体轴上有偏向。利用基于随机代理的胚胎发生模型和LoxCode条形码，该课题组人员推断并实验验证了组织间的细胞命运偏差，这些偏差符合共享和分离的分化轨迹。单细胞读数揭示了许多外胚层贡献不对称的例子，包括左胚层对右胚层和肾胚层对性腺的命运。LoxCode条形码使克隆命运分析能够用于研究小鼠生物学中的发育和更广泛的克隆问题。

据介绍，关于哺乳动物外胚层细胞的克隆命运，仍有许多有待研究。

附：英文原文

Title: LoxCode in vivo barcoding reveals epiblast clonal fate bias to fetal organs

Author: Tom S. Weber, Christine Biben, Denise C. Miles, Stefan P. Glaser, Sara Tomei, Cheng-Yu Lin, Andrew Kueh, Martin Pal, Stephen Zhang, Patrick P.L. Tam, Samir Taoudi, Shalin H. Naik

Issue&Volume: 2025-05-15

Abstract: Much remains to be learned about the clonal fate of mammalian epiblast cells. Here, we develop high-diversity Cre recombinase-driven LoxCode barcoding for in vivo clonal lineage tracing for bulk tissue and single-cell readout. Embryonic day (E) 5.5 pre-gastrulation embryos were barcoded in utero, and epiblast clones were assessed for their contribution to a wide range of tissues in E12.5 embryos. Some epiblast clones contributed broadly across germ layers, while many were biased toward either blood, ectoderm, mesenchyme, or limbs, across tissue compartments and body axes. Using a stochastic agent-based model of embryogenesis and LoxCode barcoding, we inferred and experimentally validated cell fate biases across tissues in line with shared and segregating differentiation trajectories. Single-cell readout revealed numerous instances of asymmetry in epiblast contribution, including left-versus-right and kidney-versus-gonad fate. LoxCode barcoding enables clonal fate analysis for the study of development and broader questions of clonality in murine biology.

DOI: 10.1016/j.cell.2025.04.026

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00461-1