Single-cell Systems Biology Approaches to Stem Cell Research and Regenerative Medicine
Antonio del Sol Mesa
Computational Biology Group of LCSB University, Luxembourg
The application of Systems Biology approaches to Stem Cell research is becoming more and more necessary in order to address a variety of fundamental questions in this field. In particular, with advances in single cell sequencing techniques, it is possible to get a deeper understanding of heterogenous cellular populations. However, the identification of optimal gene sets, whose perturbations can trigger specific cell population shifts, is a challenge in the application of cellular conversion strategies to regenerative medicine. In this talk, I will present computational approaches based on single-cell data, developed in our lab for the identification of optimal cellular reprogramming and differentiation determinants (transcription factors and signaling molecules).
In particular, one of the methods, which relies on information theory concepts, aims at identifying synergistic transcriptional identity cores characterizing cell subpopulations. Perturbations of these core transcription factors is shown to induce transitions between cellular subpopulations of heterogeneous stem cell populations. Our computational predictions have been experimentally validated in different cellular systems. Finally, I will discuss a recently implemented computational method that integrates cellular signaling and gene regulatory networks to identify key signaling pathways controlled by the niche to maintain specific cellular phenotypes, which could trigger cellular transitions in-vivo. This method can facilitate mimicking the niche effect on stem cell states with potential applications in regenerative medicine.
In summary, our computational predictions not only have been shown to be useful in guiding experimental research, but are currently being used in designing strategies for cell therapy treatment in patients with Parkinson's disease, as well as in patients with partial vision loss due to depletion of corneal limbus stem cells.
Host: Amanda Sierra
This seminar is partially supported by the Campus of Biscay of the UPV/EHU.