Department of Chemistry, Tsinghua University, Beijing, 100084, China.
Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
J Am Soc Mass Spectrom. 2019 Dec;30(12):2646-2654. doi: 10.1007/s13361-019-02334-z. Epub 2019 Oct 18.
Lipids exert substantial influences on vertebrate embryogenesis, but their metabolic dynamics at detailed structural levels remains elusive, primarily owing to the lack of a tool capable of resolving their huge structural diversity. Herein, we present the first large-scale and spatiotemporal monitoring of unsaturated lipids with C=C specificity in single developing zebrafish embryos enabled by photochemical derivatization and tandem mass spectrometry (MS). The lipid isomer composition was found extremely stable in yolk throughout embryogenesis, while notable differences in ratios of C=C location (e.g., PC 16:0_16:1 (7) vs. 16:0_16:1 (9)) and fatty acyl composition isomers (e.g., PC 16:1_18:1 vs. 16:0_18:2) were unveiled between blastomeres and yolk from zygote to 4 h post fertilization (hpf). From 24 hpf onwards, lipid isomer compositions in embryo head and tail evolved distinctively with development, suggesting a meticulously regulated lipid remodeling essential for cell division and differentiation. This work has laid the foundation for functional studies of structurally defined lipids in vertebrate embryology.
脂质对脊椎动物胚胎发生有很大的影响，但由于缺乏能够解析其巨大结构多样性的工具，其代谢动力学在详细的结构水平上仍然难以捉摸。本文通过光化学衍生化和串联质谱（MS），首次在单个发育中的斑马鱼胚胎中对具有 C=C 特异性的不饱和脂质进行了大规模、时空监测。研究发现，在整个胚胎发生过程中，卵黄中的脂质异构体组成极其稳定，而合子到 4 小时后（hpf），卵裂球和卵黄中 C=C 位置（例如 PC 16:0_16:1 (7) 与 16:0_16:1 (9)）和脂肪酸酰基组成异构体（例如 PC 16:1_18:1 与 16:0_18:2）的比例存在显著差异。从 24 hpf 开始，胚胎头部和尾部的脂质异构体组成随发育而显著进化，表明精细调控的脂质重塑对于细胞分裂和分化至关重要。这项工作为脊椎动物胚胎学中结构定义脂质的功能研究奠定了基础。
