Metabolic Plasticity in Stem Cell Homeostasis and Differentiation

Folmes, Clifford D.L.; Dzeja, Petras P.; Nelson, Timothy J.; Terzic, André

doi:10.1016/j.stem.2012.10.002

Cited by 577 publications

(582 citation statements)

References 100 publications

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“…Recent studies suggest the importance of metabolic transition in regulating the quiescence, activation, proliferation, and differentiation of stem cells (14,15,37). OXPHOS and glycolysis are two major metabolic pathways generating energy in mammalian cells (38).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, overactive OXPHOS exposes stem cells to reactive oxygen species and in consequence increases the risk of DNA damage, inducing mutagenesis and impairing their stemness (15). Because of these advantages of glycolysis, stem cells mainly relay on glycolysis for energy generation (13,14). However, the relatively inefficient energy generation of glycolysis poses a challenge for stem cells to sustain multiple energy demanding processes associated with stem cell activation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

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AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration

Zhu

Dodson

et al. 2015

Journal of Biological Chemistry

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Background:The mechanisms eliciting metabolic activation in satellite cells are unclear. Results: Noncanonical Sonic Hedgehog is activated following muscle injury, which activates AMPK␣1 to induce Warburg-like glycolysis and promote satellite cell activation and proliferation. Conclusion: AMPK␣1 is required for Warburg-like glycolysis in satellite cells, which promotes satellite cell activation and muscle regeneration. Significance: AMPK promotes satellite cell activation during muscle regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration

Zhu

Dodson

et al. 2015

Journal of Biological Chemistry

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“…Likewise, the observation that CBCs have an increased dependence on oxidative metabolism may seem counter to the data from studies that have shown reduced oxidative capacity in embryonic stem cells, long-term hematopoietic stem cells, mesenchymal stem cells, and hepatic stem cells [4]. However, some cancer stem cell populations have been shown to be dependent on oxidative and mitochondrial metabolism.…”

mentioning

confidence: 82%

“…Many proliferative cell types including activated lymphocytes, progenitor cells in the developing retina, cells of the preimplantation stage embryo [4], and tumor cells are highly glycolytic [5]. The correlation between high glycolytic activity and proliferation has been attributed to the increased demand for anabolic metabolism -the biosynthesis of macromoleculeswhich can be supported, in part, by increased levels of glycolytic intermediates that can be used in a number of biosynthetic reactions [5].…”

mentioning

confidence: 99%

Beyond growth signaling: Paneth cells metabolically support ISCs

Dayton

2017

Cell Res

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The small intestinal epithelium is the fastest self-renewing tissue in mammals and has served as the principle model for the study of adult stem cell biology [1]. The small intestine is structurally organized into stem cell compartments, the crypts of Lieberkühn, and functional epithelial compartments, luminal protrusions called villi that extend out from the crypts and contain specialized differentiated epithelial cell types (Figure 1A). Intestinal stem cells (ISCs), which are called crypt base columnar cells (CBCs) and express Lgr5, reside at the base of the crypts intermingled with post-mitotic Paneth cells. The close interaction of CBCs with Paneth cells is essential for maintaining the stem cell function of CBCs. In addition to secreting antibacterial peptides, Paneth cells support stem cell function through the secretion of growth signaling molecules that are required for CBC proliferation and maintenance [2].The dependence of CBCs on Paneth cell-mediated paracrine signaling can be recapitulated in vitro. Single Lgr5 + CBCs can be expanded in vitro in a 3-D, matrigel-based culture that

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“…It is therefore speculated that in stem cells, the UPR mt is activated under a physiological condition when mitochondrial biogenesis is induced. Adult stem cells frequently exit the cell cycle and are predominantly found in the quiescent (G0) state, where the number of mitochondria is low and glycolysis is the primary metabolic pathway to support energy production (Folmes, Dzeja, Nelson & Terzic, 2012; Takubo et al., 2013; Warr & Passegue, 2013; Yu et al., 2013). As stem cells transit from quiescence to proliferation, mitochondrial biogenesis is induced to enable metabolic reprogramming from glycolysis to oxidative phosphorylation to meet increasing energy demands.…”

Section: Introductionmentioning

confidence: 99%

The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence

et al. 2018

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SummaryThe mitochondrial unfolded protein response (UPR mt), a cellular protective program that ensures proteostasis in the mitochondria, has recently emerged as a regulatory mechanism for adult stem cell maintenance that is conserved across tissues. Despite the emerging genetic evidence implicating the UPR mt in stem cell maintenance, the underlying molecular mechanism is unknown. While it has been speculated that the UPR mt is activated upon stem cell transition from quiescence to proliferation, the direct evidence is lacking. In this study, we devised three experimental approaches that enable us to monitor quiescent and proliferating hematopoietic stem cells (HSCs) and provided the direct evidence that the UPR mt is activated upon HSC transition from quiescence to proliferation, and more broadly, mitochondrial integrity is actively monitored at the restriction point to ensure metabolic fitness before stem cells are committed to proliferation.

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Metabolic Plasticity in Stem Cell Homeostasis and Differentiation

Cited by 577 publications

References 100 publications

AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration

AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration

Beyond growth signaling: Paneth cells metabolically support ISCs

The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence

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