Gene regulation of stem cell fates
Animals rely on stem cells for tissue growth, repair, and remodeling. These cells need to self-renew to produce more daughter stem cells and differentiate to generate a variety of differentiated cell types. How is the identity of stem cells, or 'stemness', defined? How are self-renewal and differentiation coordinated in order to maintain the stability and dynamics of stem cell populations? How did the genetic programs of stem cells evolve? We use functional genomic analysis to study gene regulatory networks that govern stem cell fate choices 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, along with their evolutionary relatives.
Read more: Wang et al. eLife, 2018 | Li et al. Nature Communications, 2021
Comparative systems biology of regeneration
Although all animals can heal wounds, only some are capable of regenerating from major tissue losses. The ability to regenerate all body parts (whole-body regeneration) is one of the greatest mysteries in biology. To achieve control over this process would be a moonshot triumph for bioengineering. We use state-of-the-art single-cell multiomic sequencing and functional genomic analysis to (1) reconstruct cell type-specific gene regulatory networks in response to injury and (2) to compare them across 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: Tarashansky et al. eLife, 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.