Sirtuins in metabolism, stemness and differentiation

Pluripotent stem cells promise innovative approaches for enduring diseases, including disease modeling and drug screens. Accordingly, efforts have been undertaken in order to efficiently reprogram somatic cells to pluripotency, and then differentiate them into pure cultures of specific cell lineages. However, the latter step remains mostly elusive, and, in order to better control differentiation and design more efficient differentiation strategies, the cellular mechanisms behind different pluripotency stages that mimic embryonic development are being actively addressed.

Metabolism is one of many cellular processes that are in constant adjustment during mammalian embryo development, as well as in pluripotent stem cell establishment and differentiation. Thus, the role of molecular pathways known to be involved in metabolic control has been recently addressed as potential modulators of pluripotency. Notably, mammalian sirtuins have emerged as master regulators of many cellular processes, including epigenetics and metabolism. In this review we address the potential developmental role of sirtuins, with a particular focus on sirtuin 1.

This review focuses on the most recent studies implying sirtuins as regulators of pluripotency and differentiation of pluripotent stem cells, highlighting metabolic control as associated with the control of pluripotency. It notably stresses the role of sirtuin 1 in these processes, creating parallels between in vitro manipulations and developmental cues.

Using metabolic control in order to determine cellular fate, both in terms of somatic cell reprogramming to pluripotency and pluripotent stem cell differentiation, is a topic of increasing interest, and sirtuins are key players in these efforts.