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Integrating metabolic and epigenetic regulation in mesenchymal stem cells

Peter Tessarz
Max Planck Institute for Biology of Ageing
Cologne

Phone: +49 221 / 37970 680         
E-mail: peter.tessarzSpamProtectionage.mpg.de
For more information and contact please visit the TESSARZ LAB.

Abstract
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.

Latest publication

Pouikli A, Maleszewska M, Parekh S, Yang M, Nikopoulou C, Bonfiglio JJ, Mylonas C, Sandoval T, Schumacher A-L, Hinze Y, Matic I, Frezza C and Tessarz P (2022).Hypoxia promotes osteogenesis via regulating the acetyl-CoA-mediated mito-nuclear communication. EMBO J, e111239 

Pouikli A, Parekh S, Maleszewska M, Baghdadi M, Tripodi I, Nikopoulou C, Folz-Donahue K, Hinze Y, Mesaros A, Giavalisco P, Dowell R, Partridge L, Tessarz P (2021): Chromatin remodeling due to degradation of citrate carrier impairs osteogenesis of aged mesenchymal stem cells. Nature Aging 1, 810–825

Pouikli A and Tessarz P (2021). Metabolism and Chromatin: A Dynamic Duo that Regulates Mesenchymal Stem Cell Biology in Development and Ageing. BioEssays, 43 (5):e2000273.

Tessarz, P., Santos-Rosa. H., Robson. S., Sylvestersen, K.B., Nelson . C., Nielsen. M.L., and Kouzarides. T. (2014). Glutamine methylation on histone H2A is an RNA Polymerase I dedicated modification. Nature 505, 564-568.