Molecular mechanism underlying the difference in proliferation between placenta-derived and umbilical cord-derived mesenchymal stem cells

The placenta and umbilical cord are pre-eminent candidate sources of mesenchymal stem cells (MSCs). However, placenta-derived MSCs (P-MSCs) showed greater proliferation capacity than umbilical cord-derived MSCs (UC-MSCs) in our study. We investigated the drivers of this proliferation difference and elucidated the mechanisms of proliferation regulation. Proteomic profiling and Gene Ontology (GO) functional enrichment were conducted to identify candidate proteins that may influence proliferation. Using lentiviral or small interfering RNA infection, we established overexpression and knockdown models and observed changes in cell proliferation to examine whether a relationship exists between the candidate proteins and proliferation capacity. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence assays were conducted to elucidate the mechanisms underlying proliferation. Six candidate proteins were selected based on the results of proteomic profiling and GO functional enrichment. Through further validation, yes-associated protein 1 (YAP1) and beta-catenin were confirmed to affect MSCs proliferation rates. YAP1 and beta-catenin showed increased nuclear colocalization during cell expansion. YAP1 overexpression significantly enhanced proliferation capacity and upregulated the expression of both beta-catenin and the transcriptional targets of Wnt signaling, CCND1, and c-MYC, whereas silencing beta-catenin attenuated this influence. We found that YAP1 directly interacts with beta-catenin in the nucleus to form a transcriptional YAP/beta-catenin/TCF4 complex. Our study revealed that YAP1 and beta-catenin caused the different proliferation capacities of P-MSCs and UC-MSCs. Mechanism analysis showed that YAP1 stabilized the nuclear beta-catenin protein, and also triggered the Wnt/beta-catenin pathway, promoting proliferation.