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Published on: February 27, 2016
Sirtuins in metabolism, stemness and differentiation
Marcelo Correia1, Tânia Perestrelo2, Ana S Rodrigues3
1Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine (PDBEB), CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal.
Background:
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.
Scope Of Review:
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.
Major Conclusions:
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.
General Significance:
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.
Insights
Sirtuins, particularly sirtuin 1, are key regulators of cellular metabolism and epigenetics. These proteins play a crucial role in controlling pluripotency and differentiation of stem cells, offering new avenues for regenerative medicine and disease research.
Area of Science:
- Cell Biology
- Developmental Biology
- Metabolic Regulation
Background:
- Pluripotent stem cells offer potential for treating diseases via disease modeling and drug screening.
- Efficient reprogramming of somatic cells to pluripotency and subsequent differentiation into specific cell lineages are key challenges.
- Understanding the cellular mechanisms governing pluripotency stages, mimicking embryonic development, is crucial for improving differentiation strategies.
Purpose of the Study:
- To review the role of sirtuins in regulating pluripotency and differentiation of pluripotent stem cells.
- To highlight the association between metabolic control and pluripotency regulation.
- To emphasize the specific role of sirtuin 1 in these processes, drawing parallels between in vitro and in vivo systems.
Main Methods:
- Literature review of recent studies on sirtuins, pluripotency, and stem cell differentiation.
- Focus on studies investigating the metabolic control aspects of pluripotency.
- Analysis of sirtuin 1's function in pluripotent stem cells and during differentiation.
Main Results:
- Sirtuins emerge as master regulators of cellular processes, including epigenetics and metabolism.
- Metabolic pathways are increasingly recognized as modulators of pluripotency.
- Sirtuin 1 is implicated as a significant regulator in stem cell pluripotency and differentiation, linking metabolic control to developmental cues.
Conclusions:
- Metabolic control is a critical determinant of cellular fate in somatic cell reprogramming and stem cell differentiation.
- Sirtuins are central players in harnessing metabolic control for reprogramming and differentiation.
- Further research into sirtuins, especially sirtuin 1, is essential for advancing stem cell therapies and understanding developmental biology.
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