Editors' ChoiceDevelopmental Biology

Metabolites drive cell fate in the developing embryo

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Sci. Signal.  09 Jun 2015:
Vol. 8, Issue 380, pp. ec152
DOI: 10.1126/scisignal.aac7326

During early embryonic development, each cell gives rise to a different organ type. Because some early embryonic cells—blastomeres of the 16-cell Xenopus laevis embryo, for example—are transcriptionally and translationally silent, changes in metabolites may contribute to the establishment of specific cell fates. Onjiko et al. employed single-cell CE-µESI-MS (capillary electrophoresis-micro flow electrospray ionization mass spectrometry) to monitor metabolites in three different cell types of 16-cell Xenopus embryos: the midline dorsal-animal cell (D11), which gives rise to the retina and brain; the midline ventral-animal cell (V11), which gives rise to the head and the epidermis of the trunk; and the midline ventral-vegetal cell (V21), which gives rise to the hindgut. Mass spectrometry analysis revealed the molecular identity of 40 of these metabolites. Unsupervised hierarchical cluster analysis of the identified metabolites revealed that each of the cell types could be distinguished by metabolic profile, and cells of different types had different ratios of specific metabolites. Exposure of embryos to ultraviolet (UV) radiation disrupts brain development. Metabolite analysis of UV-treated embryos revealed decreased serine, glycine, and threonine amino acids along with urocanate-hypoxanthine in the D11 cells, suggesting a direct role of these metabolites in brain development. Similarly, microinjection of metabolites into the cell types that would normally have them in lower abundance perturbed the development of their respective tissues. Thus, this study not only provides a methodology for measuring small metabolites in individual cells, but also indicates that metabolite changes play important roles in cell fate decisions in the developing embryo.

R. M. Onjiko, S. A. Moody, P. Nemes, Single-cell mass spectrometry reveals small molecules that affect cell fates in the 16-cell embryo. Proc. Natl. Acad. Sci. U.S.A. 112, 6545–6550 (2015). [Abstract] [Full Text]