Single-cell genetic and epigenetic determinants of developmental potential

 Stem cells play critical roles in tissue development, maintenance, and repair (Sozen et al., 2021). Their ability to self-renew and differentiate into more specialized cell types, given the appropriate signals and regulatory programs, make them promising candidates for regenerative medicine (Wu and Hochedlinger 2011). However, potency – the capacity of a stem cell to create more specialized cells within a developmental continuum, remains poorly understood. In our lab we seek to uncover the patterns that regulate stem cell potency across tissue types, toward harnessing our findings to better understand human diseases, such as cancer, where altered developmental hierarchies play a role. To this end, I am applying SCENIC, a computational method that infers gene regulatory networks from single-cell RNA sequencing (scRNA-seq) data (Aibar et al., 2017), to analyze publicly available datasets of developmental systems with experimentally-confirmed potency levels. With this approach, I am delineating transcription factors that may regulate distinct stem cell potency levels, both across datasets of a given tissue type and across tissue types. Additionally, I am exploring chromatin accessibility data (single-cell ATAC-seq) to provide insight into the epigenetic underpinnings of developmental potential. By completing these aims, we hope to attain a better understanding of the genetic and epigenetic factors that control stem cell potency, with the ultimate goal of advancing stem cell-based therapies for regenerative medicine and oncology.