Cellular Reprogramming and Aging
In this chapter, we will discuss how aging impacts the dynamics of stem cells and affects cellular reprogramming. We will discuss certain pathways involved in the aging process, and how we can use those pathways to increase the efficiency of the reprogram
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Cellular Reprogramming and Aging Sandrina Nóbrega-Pereira and Bruno Bernardes de Jesus
Contents 5.1
Stem Cells in Health and Disease – 74
5.1.1
Aging of Stem Cells – 75
5.2
Cellular Reprogramming – 77
5.2.1 5.2.2
ging as a Barrier for Cellular Reprogramming – 78 A Reprogramming In Vivo as an Antiaging Strategy – 84
References – 86
© Springer Nature Switzerland AG 2020 G. Rodrigues, B. A. J. Roelen (eds.), Concepts and Applications of Stem Cell Biology, Learning Materials in Biosciences, https://doi.org/10.1007/978-3-030-43939-2_5
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S. Nóbrega-Pereira and B. B. de Jesus
What Will You Learn in This Chapter? In this chapter, we will discuss how aging impacts the dynamics of stem cells and affects cellular reprogramming. We will discuss certain pathways involved in the aging process, and how we can use those pathways to increase the efficiency of the reprogramming protocol. Furthermore, we will describe two protocols to establish primary cultures of a “young” cell line (mouse embryonic fibroblasts—MEFs) and an adult/old cell line (primary cultures of adult/old mouse ear fibroblasts). These cell lines are often the primary choice to study aging in vitro.
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5.1
Stem Cells in Health and Disease
Stem cells are defined as cells that retain the potential to differentiate into several cell lineages and have a constant self-renewal capacity, although with a limited replicative capacity in vivo [1]. Three criteria should be met: (i) a stem cell should be able to selfrenew, (ii) it should be unspecialized, meaning that it should not perform any function until required, and (iii) a stem cell should be able to specialize/differentiate into at least one cell type. One of the best-characterized pools are the stem cells belonging to the hematopoietic system (hematopoietic stem cells—HSC). These cells can differentiate in blood cells and are crucial for the normal functioning of the young and adult hematopoietic system. HSC follow a hierarchical cascade where multipotent stem cells give rise to fully committed lineages [1]. This traditional view has been challenged recently, and it has been hypothesized that stem cells, although residing at an organ-specific niche, can trans-differentiate to cell types, including cells from a different lineage. While the mechanism remains poorly understood and the field controversial, this could have implications for organ renewal [2]. Different tissues have variable rates of proliferation. In tissues with high proliferative capacity, stem cells were shown to generate large amounts of progeny, whereas in tissues with lower proliferative potential, it is believed that stem cells have less critical functions; recent evidence demonstrate, however, that almost every tissue (including heart and brain) retains fully functional niches of pluripotent cells which can replace damaged cells [3–8]. The safeguarding of these cell niches is crucial for the maintenance of body function, in particular, at older ages when tissues are more receptive to damaging signals. Indeed, mice w
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