Noncoding RNA regulatory networks, epigenetics, and programming stem cell renewal and differentiation

Stem cells play a vital role in the development, maintenance, and repair of tissues and organs and hold significant promise for tissue repair after injury and disease, and for the cure of degenerative diseases. However, fulfilling the therapeutic potential of stem cell therapy requires that we understand and effectively manage cell-, tissue-, and even organism-specific programs that guide stem cell maturation alongside key biological variables that impact these programs, like genetic sex. In this chapter, we briefly highlight evidence for a core network of genes that control stem cell renewal and maturation. We then focus on emerging evidence for a novel and evolutionary diverse layer of cell regulation, termed “epigenetics,” that controls the fate of stem cells. We also explore emerging evidence for a vast regulatory network of non-protein–coding RNA (ncRNA) molecules that participate in stem cell renewal and differentiation. The integrative role of epigenetics and ncRNA networks makes understanding these mechanisms in tandem key to utilize stem cell programming for clinical therapies.