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. 2019 Nov 5;9:16054. doi: 10.1038/s41598-019-52372-6

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Metabolomic profiles of livers and brains from wild-type and Shmt2-knockout E13.5 embryos. (a) PCA of livers and brains to compare metabolomic data between wild-type and Shmt2-knockout E13.5 embryos. WT, wild-type foetal livers (closed blue circles), wild-type foetal brains (open blue circles); KO, Shmt2-knockout foetal livers (closed red circles), Shmt2-knockout foetal brains (open red circles). (b) Volcano plots of metabolomic changes caused by Shmt2 knockout in livers and brains from E13.5 embryos. Broken lines, threshold of significance; red dots, serine; blue dots, glycine; orange dots, threonine; black dots, metabolites exhibiting significant changes; grey dots, metabolites without significant changes. (c) Pathway analysis of metabolomic changes caused by Shmt2 knockout in livers and brains from E13.5 embryos. Broken lines, threshold of significance; black dots, pathways with significant changes; red dots, pathways involved in 1C metabolism with significant changes, including taurine metabolism, purine metabolism, pyrimidine metabolism, and glycine, serine, and threonine metabolism; and grey dots, pathways without significant changes. Pathway impact represents a combination of the centrality and pathway enrichment results. (d) A scheme of mitochondrial 1C metabolism in the livers of Shmt2-knockout E13.5 embryos. A red character denotes a metabolite that increased; a blue character denotes a metabolite that decreased; a black character denotes a metabolite that was unchanged in foetal liver without functional Shmt2; grey characters denote metabolites not quantified in this study. THF, tetrahydrofolate; 5,10-me-THF, 5,10-methylenetetrahydrofolate; τ m5U, 5-taurinomethyluridine; fMet, formylmethionine. (e) Effects of Shmt2 knockout on concentrations of serine, glycine, and threonine in livers or brains from E13.5 embryos. WT, wildtype foetal livers (filled blue bars) and wild-type foetal brains (open blue bars); KO, Shmt2-knockout foetal livers (filled red bars) and Shmt2-knockout foetal brains (open red bars). Data represent the mean ± S.D. *P < 0.05; **P < 0.01, ***P < 0.001 (WT, n = 5; KO, n = 5).