Integrating metabolic and epigenetic regulation in mesenchymal stem cells
Endosteum-derived mesenchymal stem cells (MSCs) reside in a hypoxic niche (~2% oxygen levels) and have the capacity to differentiate into adipocytes, chondrocytes and osteoblasts. Based on this potential, MSCs have long been regarded as a potential therapeutic agent, e.g. in osteoporosis patients. Early clinical trials are under way to assess the feasibility of stem cell therapies using MSCs. However, one problem is the fact that MSCs lose potential in elderly patients and also, when cultured for a prolonged time under atmospheric oxygen concentration. During differentiation, MSCs switch their metabolism from anaerobic glycolysis to OXPHOS. In this project we aim at understanding how the hypoxic niche preserves the potency of the cells and how this is shaped by the interplay of metabolism and epigenetics.
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