The Role of Transposable Elements in the Differentiation of Stem Cells

Аннотация

The activation of mobile genetic elements is a prerequisite for controlling the expression of genes in successive cell divisions, with their change specifically depending on the tissue and developmental stage. These activation patterns are characteristic of totipotent and pluripotent embryo cells, as well as for stem cells in the postnatal period. We have suggested that in the evolution of multicellular eukaryotes, optimal ratios are selected in the arrangement of transposons relative to exons and introns of host genes. These ratios, specific to each species, can be the basis for controlling the sequential differentiation of stem cells necessary for the development of the whole organism. Despite the fact that cell differentiation in ontogenesis is controlled by a very conservative set of genes, mobile genetic elements are involved in the fine-tuning of regulatory networks that control the expression of these genes, which is reflected in the phenotypic characteristics of each species. Transposons are important sources of genome structures that are actively used to regulate the multicellular embryonic development. These structures include binding sites with transcription factors, enhancers and silencers, promoters, insulators, alternative splicing sites, non-coding RNA. Moreover, transposons are involved in the emergence and evolution of new protein-coding genes through exonization, domestication, and the formation of retrogenes. The activation of transposons is needed to regulate the differentiation and reproduction of cells in the body; however, in terminally differentiated cells, upon reaching predetermined sizes of organs, molecular systems are activated that block a further cascade of transposon activation. We suggest that the imperfection of systems aimed at specific suppression of transposon activity in mature cells may be the cause of aging and age-related diseases due to the pathological activation of mobile genetic elements. Identifying the tissue-specific mechanisms of inherited transposon activation in stem cells, as well as their pathological activation in terminally differentiated cells, may be the basis for finding ways to fight aging.