PhD Candidate Amsterdam UMC Location University of Amsterdam, Netherlands
Abstract: Primordial germ cells (PGCs) are the embryonic precursors of gametes and play a crucial role in reproductive biology. The in vitro differentiation of human PGC-like cells (hPGCLCs) from induced pluripotent stem cells (hiPSCs) offers a valuable model for studying germ cell development and potential applications in regenerative medicine. However, a detailed understanding of the molecular differences between hiPSCs and their differentiated hPGCLC counterparts remains elusive, particularly in terms of their proteomic and metabolomic profiles. While genomics offers valuable information on genetic potential, ; proteomics and metabolomics offer crucial insights into the functional state of cells, allowing for a more accurate representation of their phenotype and physiological state. With the goal of characterizing the proteomic and metabolomic changes during early hPGCLC induction, we employed a multi-omics approach that combined metabolomics and proteomics mass spectrometry. For this, we performed a previously published hPGCLC in vitro differentiation protocol, and collected for analysis the progenitor hiPSCs and the differentiated hPGCLC and non-hPGCLC fraction, as a differentiation-effect control. The results showed distinct metabolic and proteomic profiles between the progenitor cells and differentiated counterparts, and a distinct proteomic profile between hPGCLCs and the non-hPGCLC fraction. Several alterations were detected in the glycolysis pathway and oxidative phosphorylation (citric acid cycle and the electron transport chain), between the three groups. The data indicate that the hPGCLCs present a more quiescent energy state, with decreased oxidative phosphorylation in comparison to hiPSCs and non-hPGCLCs, and a decreased glycolytic activity versus non-hPGCLC. The integration of a multi-omics approach study not only contributes to the fundamental characterization of iPSC-derived PGCLCs, but also offers potential insights for optimizing in vitro differentiation protocols that are needed to generate human gametes from stem cells in vitro. Moreover, it may provide a more inclusive understanding of the biological processes underlying human PGC differentiation in general.
Funding Source: This study was funded by ZonMW PSIDER 10250022120001.
