Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, ON, Canada.
FEBS J. 2021 Jun;288(11):3394-3406. doi: 10.1111/febs.15598. Epub 2020 Oct 28.
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.
许多动物物种都有干细胞，这些干细胞在它们的一生中都能维持，这表明干细胞是所有动物的祖先特征。由此，我们认为具有“干性”-自我更新和多能性的生物学特性的细胞可能具有共同的祖先遗传回路。然而，在实践中，很难识别和比较不同动物和大进化距离之间的干性基因特征？首先，必须通过实验证明自我更新和潜能。其次，必须使用基因组方法来确定干细胞类型与非干细胞类型之间的特定基因表达，以确定干细胞基因富集。第三，必须在大进化距离的不同动物之间映射基因同源性。最后，必须测试满足这些标准的保守基因在干细胞功能中的作用。我们的观点是，通过比较进化过程中的干细胞特异性基因特征，可以揭示干性的祖先程序，最终，干性程序的失调导致癌症干细胞状态。
