One stem cell program to rule them all?

The ancestral origins of adult stem cells (ASCs) suggest that ASCs of diverse animals may share gene regulatory circuitry. By comparing homologous gene expression between the ASCs of many species, it is our viewpoint that a shared stemness signature can be detected. We propose that conserved stemness genes are also dysregulated in cancers that are driven by cancer stem cells. Many species of animals have stem cells that they maintain throughout their lives, which suggests that stem cells are an ancestral feature of all animals. From this, we take the viewpoint that cells with the biological properties of ‘stemness’—self‐renewal and multipotency—may share ancestral genetic circuitry. However, in practice is it very difficult to identify and compare stemness gene signatures across diverse animals and large evolutionary distances? First, it is critical to experimentally demonstrate self‐renewal and potency. Second, genomic methods must be used to determine specific gene expression in stem cell types compared with non‐stem cell types to determine stem cell gene enrichment. Third, gene homology must be mapped between diverse animals across large evolutionary distances. Finally, conserved genes that fulfill these criteria must be tested for role in stem cell function. It is our viewpoint that by comparing stem cell‐specific gene signatures across evolution, ancestral programs of stemness can be uncovered, and ultimately, the dysregulation of stemness programs drives the state of cancer stem cells.