Resident Sox2+ cells are the cell of origin for neuroendocrine tumors

While as a practical matter it is common in the laboratory to define cells by general descriptions of gene expression (e.g. Sox2+ or Sox-) in living systems we recognize that each cell is different, and therefore has a slightly different identity from other cells classified in the same type. We believe that this cellular variability plays a large role in why some cells are capable of forming a tumor while other cells, even with the same causative mutations, do not.

We have identified that in “normal” neuroendocrine cells there is a variable expression of Sox2. While Sox2 is repressed in the bulk of the cells, some show indications of Sox2 de-repression. We are currently investigating if it is these Sox2 de-repressed cells that form tumors when Rb is lost. Furthermore we will investigate if this de-repression is developmental or epigenetic in nature. We will accomplish this by utilizing the latest single-cell technologies and in vivo lineage tracing experiments. Finally we will evaluate the means by which cells restrict Sox2 variability with the long-term goals of inhibiting tumors or enhancing regeneration.