The Atwood lab is interested in how stem cell heterogeneity drives epidermal homeostasis and disease. We focus on protein kinase regulation of signaling pathways and transcription factors, using models of skin development and basal cell carcinoma, to determine how kinases influence cell fate by controlling the genetic landscape of the cell.
We use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models. Knockdown of some differentially expressed basal stem cell genes result in severe thinning of human skin equivalent organoids, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.
Nature Communications. 11(1): 4239. https://doi.org/10.1038/s41467-020-18075-7. Link PDF