Modelling the Gene Regulatory Network underlying Lineage Commitment in Human Mesenchymal Stem Cells (LINCONET)

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With the aging of the world population, degenerative diseases such as osteoporosis and arthritis will have an increasing impact on health and quality of life. Restoration of damaged bone and cartilage by stimulating human mesenchymal stem cells (HMSCs) to differentiate into bone- or cartilage-synthesizing cells provides a novel and attractive therapeutic opportunity with profound implications in biomedicine. This requires a thorough understanding of the normal biological processes underlying cell differentiation and the disease-induced tissue degeneration. Given the multi-potent character of stem cells, and the complexity of the cross-talk between signalling pathways that determine lineage commitment and disease progression, an integrated approach that uses advanced computational techniques (a systems biology approach) is essential. This project aims to develop a framework to understand tissue regeneration. To this end, we will unravel and mechanistically model the genetic network underlying normal tissue regeneration processes. An integral part of our strategy is to experimentally validate hypotheses generated by computational models by using tightly integrated cycles of computational modelling and experimental verification at the cellular and organism level.