Characterization of the metabolome and proteome of stem cell-derived human primordial germ cell-like cells: a multi-omics approach

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Primordial germ cells (PGCs) are the population of cells that, in the human embryo, are initially specified at day 12 post-fertilization, and form the precursor cells for the future gametes. Although in vitro differentiation of PGCs from human stem cells has been achieved, these primordial germ cell-like cells (hPGCLCs) fail to completely mature without the use of ex vivo human or animal gonadal soma. Previous studies in mice revealed that several metabolic changes occur during the specification and maturation of these cells, which are essential for their developmental progress. However, little is known about the metabolic profile of human primordial germ cells. In the scarcity of human PGCs, particularly at the early specification stage, hPGCLCs serve as a research model to study PGC formation. To characterize the metabolic and proteomic profile of these cells, we differentiated hPGCLCs using induced-pluripotent stem cells and performed a mass spectrometry analysis to establish their metabolome and proteome. These cells revealed distinct metabolic profile, with changes particularly at the proteome level. This included a shift between canonical and non-canonical citric acid cycle in hPGCLCs, downregulation of late-stage glycolysis and reduction of nucleotide de novo synthesis. By providing an integrative map of these metabolic networks, we aim to provide insight on the metabolism of hPGCLC development that could help improve methods for fully in vitro differentiation and maturation of hPGCLCs.