(317b) Skin Tissue Derived Neural Crest Stem Cells and Metabolic Requirements for Multipotency
AIChE Annual Meeting
Tuesday, November 15, 2022 - 12:48pm to 1:06pm
In this regard, we mimicked the developmental microenvironment during NC induction and treated the cells with BMP2 and the Wnt agonist CHIR99021 to preserve multipotency of KC-NCs. 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 KC-NCs 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 KC-NCs, which increased lactate production, glucose consumption and sensitivity to insulin stimulation. Energy demands of multipotent KC-NCs were evaluated by employing the Seahorse ATP Rate assay. Indeed, cells treated with CHIR/BMP2 derived most of their ATP from glycolysis, and the mitochondrial activity was diminished. Taken, together, this study elucidates how developmental events control the carbon metabolism and bioenergetics state of NCs, which is important in understanding metabolic disorders arising from dysregulation of NC induction and differentiation during embryogenesis. We also describe a simple method using a cocktail of chemicals and growth factors for maintaining KC-NC multipotency for treatment of demyelinating and other diseases.