Stem Cells Seen Through the FOXO Lens: An Evolving Paradigm.

Stem cells self-renew and differentiate to generate all tissues and cells in the body. Stem cell health promotes adaptive responses to tissue damage or loss and is essential for tissue regeneration with age. In the past decade, the evolutionarily conserved transcription factors FOXO with known functions in promoting healthy aging have emerged as key regulators of stem cell homeostasis in various tissues, including blood, neural, and muscle stem cells. Aberrant FOXO functions have been implicated in a variety of disorders including neurodegenerative, blood, cancer, and diabetes some of which are fostered by abnormal stem cell function. As discussed in this chapter, at least in some stem cells FOXO regulatory mechanisms and applied functions follow a complex set of rules distinct from that operating in progenitor cell populations and in cultured cell lines. Elucidating the exact nature of FOXO properties in stem cells will be critical for identifying and targeting aberrant FOXO-mediated mechanisms that promote stem cell-derived disease specifically with age.