Analysis of gene expression in stem cells: FOXO transcription factors as master regulators of stemness

Abstract

Nowadays, it exist the necessity to understand the intrinsic mechanism that governs stem cells which constitutes a regeneration system. The expression of genes, transcription factors, microRNAs and pathways acting as a regulators enable that stem cells work properly, this elements are the responsible of the particular behavior and as a consequence allow that stem cells present the capacity of self-renewal. It is useful to work and analyze the expression of these elements in order to understand specific mechanisms present in stem cells, for this purpose we implemented a comparative analysis of global gene expression and also it is realized through different programs a analysis of the elements acting behind these genes that are transcription factors, microRNAs and pathways. The results reveals the existence of a common element, which is FOXO3 transcription factor, present in all the types of stem cells and in different species including immortal Hydra, an organism that presents indefinite self-renewal, this fact allow to make the assumption that FOXO3 is a critical regulator that controls the characteristic properties of all the stem cells. We design in vitro quiescence and in vitro differentiation assays with muscular stem cells that confirm the assumption. Specifically, the deletion of FOXO3 in stem cells demonstrates that are unable to self-renew and to re-entry in quiescence, we observe that the cells present a differentiation fate that lead to complete deletion of stem cells. We demonstrate the important role of FOXO 3 transcription factor in maintenance of stem cells; also we define the function of FOXO3 that is the suppression of terminal differentiation allowing to replenish the stem cell pool. In conclusion, we discover a key element that is a master regulator on stemness and it is responsible for existence of stem cells. This particular role suggests that FOXO3 is implicated in longevity and can be a potential marker for regeneration and aging processes.