(89c) Wnt/BMP Regulates Multipotency of Neural Crest Stem Cells Via Metabolic and Epigenetic Rewiring
AIChE Annual Meeting
Monday, November 8, 2021 - 8:36am to 8:54am
In this regard, we mimicked the developmental microenvironment during NC induction and treated the cells will BMP2 and the Wnt agonist CHIR99021 to preserve multipotency of skin-derived NCSCs. Combinatorial Wnt/BMP2 signaling sustained the expression of transient NC genes including Sox10, Pax7, AP2A, HNK1 and TrkC in culture. Subsequently, this treatment enhanced the differentiation of NCSCs to melanocytes, schwann cells and smooth muscle cells, as indicated by increased expression of MITF, KROX20 and Î±SMA respectively. We discovered that Wnt/BMP signaling rewired the metabolic landscape of NCSCs to confer multipotency. This was achieved by activating anaerobic glycolysis in NCSCs treated with CHIR99021 and BMP2, which increased lactate production, glucose consumption and sensitivity to insulin stimulation. Additionally, we observed that CHIR/BMP2 treatment accelerated enzyme kinetics for the key glycolytic enzymes phosphofructokinase (PFK) and Pyruvate Kinase (PK) in NCSCs. Energy demands of multipotent NCSCs were evaluated by employing the Seahorse ATP Rate assay. Indeed, cells treated with the chemicals derived most of their ATP from glycolysis, and the mitochondrial activity was diminished. Taken, together, this study elucidates how developmental events control carbon metabolism and bioenergetics state of NCs, which is important understanding metabolic disorders arising from dysregulation of NC induction and differentiation during embryogenesis; as well as in maintaining NC multipotency for treatment of demyelinating and other diseases.