Chemo-Selective Single-Cell Metabolomics Reveals the Spatiotemporal Behavior of Exogenous Pollutants During Xenopus Laevis Embryogenesis

In-depth profiling of embryogenesis-associated endogenous and exogenous metabolic changes can reveal potential bio-effects resulting from human-made chemicals and underlying mechanisms. Due to the lack of potent tools for monitoring spatiotemporal distribution and bio-transformation behavior of dynamic metabolites at single-cell resolution, however, how and to what extent environmental chemicals may influence or interfere embryogenesis largely remain unclear. Herein, a zero-sample-loss micro-biopsy-based mass spectrometric platform is presented for quantitative, chemo-selective, high-coverage, and minimal-destructive profiling of development-associated cis-diol metabolites, which are critical for signal transduction and epigenome regulation, at both cellular level and tissue level of Xenopus laevis. Using this platform, three extraordinary findings that are otherwise hard to achieve are revealed: 1) there are characteristically different cis-diol metabolic signatures among oocytes, anterior and posterior part of tailbud-stage embryos; 2) halogenated cis-diols heavily accumulate at the posterior part of tailbud-stage embryos of Xenopus laevis; 3) dimethachlon, a kind of exogenous fungicide that is widely used as pesticide, may be bio-transformed and accumulated in vertebrate animals in environment. Thus, this study opens a new avenue to simultaneously monitoring intercellular and intraembryonic heterogeneity of endogenous and exogenous metabolites, providing new insights into metabolic remolding during embryogenesis and putting a warning on potential environmental risk. A micro-biopsy-based mass spectrometric platform is developed for in-depth and minimal-destructive characterization of cis-diol metabolites during development from cellular level (single oocytes) to tissue level (different parts of tailbud-stage embryos). The results reveal, for the first time, not only the multiscale heterogeneity of cis-diols during embryogenesis but also a posterior-preferred accumulation of halogenated cis-diols in embryos.image