Two Opposing Faces of Retinoic Acid: Induction of Stemness or Induction of Differentiation Depending on Cell-Type

Stem cells have the capacity of self-renewal and, through proliferation and differentiation, are responsible for the embryonic development, postnatal development, and the regeneration of tissues in the adult organism. Cancer stem cells, analogous to the physiological stem cells, have the capacity of self-renewal and may account for growth and recurrence of tumors. Development and regeneration of healthy tissues and tumors depend on the balance of different genomic and nongenomic signaling pathways that regulate stem cell quiescence, proliferation, and differentiation. During evolution, this balance became dependent on all-trans retinoic acid (RA), a molecule derived from the environmental factor vitamin A. Here we summarize some recent findings on the prominent role of RA on the proliferation of stem and progenitor cells, in addition to its well-known function as an inductor of cell differentiation. A better understanding of the regulatory mechanisms of stemness and cell differentiation by RA may improve the therapeutic options of this molecule in regenerative medicine and cancer.