Seminar

Systems Biology of Cellular Reprogramming

Antonio del Sol, PhD

Given the importance of cellular reprogramming for regenerative medicine, experimental purposes, and disease modelling, it becomes essential to create a methodology that systematically predicts reprogramming determinants genes that need to be perturbed in order to achieve transitions between specific cell types. Indeed, despite the significant advances in the field of cellular reprogramming, identifying optimal sets of genes triggering specific cellular transitions is not a trivial task, especially during trans-differentiation. Additionally, the reprogramming efficiency and fidelity is often low and a full understanding of the mechanisms underlying cellular reprogramming events remains elusive. Here Dr Antonio del Sol group propose a cellular transition-dependent method that identifies candidates for reprogramming determinants by focusing on stability motifs in gene regulatory networks. In particular, their method generalizes the concept of transcription factor cross-repression to systematically predict sets of genes, whose perturbations induce cellular transitions between any given pair of cell types. Furthermore, to their knowledge, this is the first method that systematically makes these predictions without prior knowledge of potential candidate genes and pathways involved, providing guidance on systems where little is known. Among other examples of cellular conversion, this method was applied to epithelial-mesenchymal transitions in breast cancer cell lines. In addition, they have also developed strategies to direct cell fate in differentiation based on the relative expression of lineage determinants. They have shown the performance of this methodology on different examples of stem cell differentiation events. Given the increasing interest of cellular reprogramming in medicine and basic research, their approach represents a useful computational methodology to assist researchers in the field in designing experimental strategies.