Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease

Beerman, Isabel; Rossi, Derrick J.

doi:10.1016/j.stem.2015.05.009

Cited by 161 publications

(131 citation statements)

References 161 publications

(225 reference statements)

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“…Epigenetic control of gene regulation through DNA and histone modifications has a pivotal role to ensure the appropriate transcriptional programmes during embryonic and adult neurogenesis (Cacci, Negri, Biagioni & Lupo, 2017) and can be misregulated in aged stem cell compartments (Beerman & Rossi, 2015). Altered epigenetic mechanisms could also be involved in age‐associated neurogenic decline, but little is known about the epigenetic changes that occur during the aging of adult NSPCs.…”

Section: Resultsmentioning

confidence: 99%

“…To date, the epigenomes of three stem cell populations have been examined upon mouse and human aging: blood stem cells, mesenchymal stem cells and muscle satellite cells (Beerman et al., 2013; Bocker et al., 2011; Bork et al., 2010; Fernandez et al., 2015; Liu et al., 2013; Sun et al., 2014). Together, these studies conclude that the stem cell epigenome is relatively stable during aging, with a small number of potentially important loci that are significantly altered (Beerman & Rossi, 2015). Genes encoding self‐renewal and differentiation factors are particularly vulnerable to age‐dependent alterations, and, although often do not have an immediate impact on transcriptional changes; they might alter the potential or future decisions of the stem cells (Beerman & Rossi, 2015).…”

Section: Introductionmentioning

confidence: 94%

“…Together, these studies conclude that the stem cell epigenome is relatively stable during aging, with a small number of potentially important loci that are significantly altered (Beerman & Rossi, 2015). Genes encoding self‐renewal and differentiation factors are particularly vulnerable to age‐dependent alterations, and, although often do not have an immediate impact on transcriptional changes; they might alter the potential or future decisions of the stem cells (Beerman & Rossi, 2015). Notably, the global epigenetic profiles have not been examined in aging NSPCs or in any aged somatic stem cell from nonmesoderm derivatives.…”

Section: Introductionmentioning

confidence: 94%

“…Attenuating the age‐associated decline in somatic stem cell function can be achieved by modulating the extracellular environment (Adler et al., 2007; Conboy et al., 2005; Villeda et al., 2011), which implicates epigenetic regulation as a key component of stem cell aging (Beerman & Rossi, 2015; O'Sullivan & Karlseder, 2012; Rando & Chang, 2012). To date, the epigenomes of three stem cell populations have been examined upon mouse and human aging: blood stem cells, mesenchymal stem cells and muscle satellite cells (Beerman et al., 2013; Bocker et al., 2011; Bork et al., 2010; Fernandez et al., 2015; Liu et al., 2013; Sun et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

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Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age‐associated neurogenic decline

et al. 2018

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SummaryAdult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age‐associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ‐derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age‐dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age‐related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age‐associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age‐related neurogenic decline.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age‐associated neurogenic decline

et al. 2018

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“…35 This understanding underscores the importance of health prevention that begins at conception and must be sustained throughout the life course. 36 Healthy life choices are understood to influence epigenetic expressions. Non-genetic regulation of aging is gaining scientific attention in an attempt to better understand the potential reversibility of epigenetic changes and the plasticity that may be harnessed when approaching aging and age-related diseases from a new angle: The main appeal of understanding the environmental non-genetic regulation of aging is to open new avenues for actionable interventions that could benefit the diseases of age.…”

Section: New Paradigms: Epigenetics and The Health Modelmentioning

confidence: 99%

Explorative healthy aging approaches fostering social innovation: thematizing life course narratives of older women participating in a documentary film

Riva¹,

Verloo

2017

Qual Res Med Healthc

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The transformative process of investigating life stories and their impact on healthy aging has only recently been explored. The relationship between hope and individual healthy aging strategies is still an under-researched area. This study contributes to filling the knowledgeability gap. The authors examine senior stories of hope and the experience of self-determination and well-being. The study documents the social learning processes of older people as they narratively search for solutions and imagine a hopeful future of healthy aging. A group of four older women participated in a semi-structured filmed interview, questioned by an academic expert. Healthy aging emerged as an important concern among all participants, confirming the need to actively learn how to age well. This exploratory research brought forth thematic clusters, orienting shared value solutions to demographic change. Qualitative research methods reinforce lifelong, collaborative learning processes that not only produce scientific literature, but also put in place relational networks that can grow and endure over time, generating social innovation. The film documented the role of hope and resilience in healthy aging.

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Why an integrated view of gene expression studies on hematopoiesis in mouse aging is better than the sum of their parts

Bystrykh

2024

FEBS Letters

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Globally, the human population is aging, with an increased proportion of people in “old age” (over 60 years). This trend leads to a growing demand in aging research, stimulating studies in animal models such as mice, fish, and invertebrates. Recently, we published a research summary on the aging of hematopoietic stem cells (HSCs) in C57BL/6 mice based on 12 gene expression datasets. Here, I discuss in greater detail the added value of taking an integrated view, rather than considering each publication separately, to determine genes involved in aging. Considerable variation exists between lists of differentially expressed (DE) genes in HSCs, comparing young and old mice. This variation can result from factors such as inconsistent definitions of “young” and “old”, technical variations and variations between laboratory mouse strains. We previously demonstrated that the variation between gene lists could be circumvented by forming a unified list of DE genes—the “aging list”—with citation indexes attached. The most frequently detected DE genes [approximately 200 most cited, which we named the “aging signature” (AS)] were highly consistent across publications. Gene Ontology classification of the AS list identified additional sources of variation between studies: one comes from the specifics of how the data are collected and analyzed; another comes from inconsistencies between how we define the gene categories. As discussed, overcoming these variations is the next challenge toward an integral approach to our systematic knowledge of the aging process.

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Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease

Cited by 161 publications

References 161 publications

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age‐associated neurogenic decline

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age‐associated neurogenic decline

Explorative healthy aging approaches fostering social innovation: thematizing life course narratives of older women participating in a documentary film

Why an integrated view of gene expression studies on hematopoiesis in mouse aging is better than the sum of their parts

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