Tissue ecology of stem cells
Animals rely on stem cells for tissue growth, repair, and remodeling. We view stem cells as self-replicating, heritable, natural selection units that can evolve independently. This raises a profound and unexplored challenge: how do systems maintain a stable, evolvable collective that emerges from independent selfish individual cells? Although the dynamics at the individual cell level can be stochastic, the collective output at the whole population level must be robust to steady homeostasis but adaptive to physiological changes, such as growth, injury repair, aging, and mutations. We use genomics and statistical modeling to study stem cell dynamics in planarian flatworms (image on the left, with stem cells labeled in yellow), which are immortal organisms with unparalleled regenerative ability throughout the animal kingdom. We aim to reveal mechanisms by which stem cells safeguard genome integrity, suppress uncontrolled cell proliferation, and evolve within individual organisms.
Comparative systems biology of regeneration
Whole-body regeneration (the ability to regenerate all body parts) is one of the greatest mysteries in biology. To achieve control over this process would be a moonshot triumph for bioengineering. Although all animals can heal wounds, only some are capable of regenerating from major tissue losses. Little is known about how most animals (including humans) have lost the ability of whole-body regeneration. Answers to this question will identify solutions to reactivate regeneration in animals with only limited regenerative ability. Using state-of-the-art sequencing techniques and functional genomic analyses, we study stem cells and their activities after injury in evolutionarily related flatworm species (image on the right, from Art Forms in Nature, Ernst Haeckel) to identify key cellular and genetic modifications that determine regeneration outcomes.
Read more: Wang et al. eLife, 2018 | Tarashansky et al. eLife, 2019 | Li et al. Nature Communications, 2021.
Quantitative biology of brain regeneration
Brain regeneration is particularly challenging compared to other tissue regeneration, as it involves not only the regeneration of a high diversity of cell types but also the reconnection of neural circuits in order to restore behavioral functions. Planarians, as one of the most primitive animals that possess a brain (image on the left, with the cell body positions of a particular neural type quantified, and indicated with spheres), can regrow a head within a week after decapitation. To gain a quantitative understanding of brain regeneration, we have developed new imaging techniques and taken the framework of statistical mechanics in order to break down the complexity in brain structures and organismal behaviors in our flatworm models.
Read more: Khariton et al. Nature Physics, 2020.