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

随着世界人口老龄化，骨质疏松症和关节炎等退行性疾病将对健康和生活质量产生越来越大的影响。通过刺激人间充质干细胞（HMSCs）分化成骨或软骨合成细胞来修复受损的骨和软骨提供了一种新颖而有吸引力的治疗机会，在生物医学上具有深远的意义。这需要对细胞分化和疾病诱导的组织变性的正常生物学过程有透彻的了解。鉴于干细胞的多能性，以及决定谱系承诺和疾病进展的信号通路之间相互作用的复杂性，采用先进的计算技术（系统生物学方法）的综合方法是必不可少的。这个项目旨在建立一个框架来理解组织再生。为此，我们将解开和机械模型的遗传网络背后的正常组织再生过程。我们策略的一个组成部分是通过在细胞和有机体水平上使用紧密集成的计算建模和实验验证周期来实验验证由计算模型产生的假设。

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.