Integrative metabolomics and proteomics analysis of human dental pulp stem cells during osteo/odontogenic differentiation

Abstract

Abstract Background Metabolism remodeling is essential for fulfilling the energetic demands and anabolic purposes that is prerequisite for new cellular state. How metabolic fluctuations coordinate and modulate the stem cell fate transition in mineralized tissue regeneration was largely unknown. The integrated metabolomic-proteomics analysis revealed dynamic metabolites and proteins profiles during osteo/odontogenic differentiation of human dental pulp stem cells (hDPSCs). Methods UHPLS-MS/MS untargeted metabolomics and DIA proteomics were utilized to reveal the dynamic metabolites and proteins profiles during osteo/odontogenic differentiation of hDPSCs. The integrative analysis of metabolome and proteome was performed to illustrate the metabolite remodeling and protein engagement during mineralization. Results A total of 194 differently expressed metabolites, and 4706 differently expressed proteins in hDPSCs were found during osteo/odontogenic differentiation. The integrated metabolomic-proteomics analysis showed close agreement in metabolism pathways. Glycolysis and TCA cycle were enhanced, accompanying by ATP molecule accumulation. Fatty acid degradation displayed highly upregulated with increased degradation enzymes to product CoA. Nucleotide and amino acid metabolism exhibited increased biosynthesis to fulfilled the demand along differentiation. Specially, glutathione metabolism was highly stimulated and may play a role in oxidation resistance. Conclusions Our study firstly gets the metabolomics-proteomics landscape of hDPSCs during osteo/odontogenic differentiation. It provided new insights into the regulatory metabolism during hDPSCs differentiation and shed light on the possibility of metabolic engineering in mineralized tissue regeneration.