Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells

Yu, Yilin; Newman, Hunter; Shen, Leyao; Sharma, Deepika; Hu, Guoli; Mirando, Anthony J.; Zhang, Hongyuan; Knudsen, John E.; Zhang, Guo Fang; Hilton, Matthew J.; Karner, Courtney M.

doi:10.1016/j.cmet.2019.01.016

Cited by 182 publications

(188 citation statements)

References 71 publications

(69 reference statements)

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“…Loss of GLS specifically in mouse skeletal stem cells reduced the amount of osteoblasts [141]. Glutaminase and transaminase-dependent glutamate conversion to a-ketoglutarate were found to be required in mouse skeletal stem cells to proliferate and differentiate into osteoblasts [141]. Thus, glutamine consumption increases in proliferating, differentiated cells and in activated, proliferating skeletal stem cells.…”

Section: Amino Acid Metabolismmentioning

confidence: 98%

“…The enzyme glutaminase (GLS) deaminates glutamine to form glutamine as the first step in glutamine catabolism. Loss of GLS specifically in mouse skeletal stem cells reduced the amount of osteoblasts [141]. Glutaminase and transaminase-dependent glutamate conversion to a-ketoglutarate were found to be required in mouse skeletal stem cells to proliferate and differentiate into osteoblasts [141].…”

Section: Amino Acid Metabolismmentioning

confidence: 98%

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The paradox of metabolism in quiescent stem cells

Coller

2019

FEBS Letters

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The shift between a proliferating and a nonproliferating state is associated with significant changes in metabolic needs. Proliferating cells tend to have higher metabolic rates, and their metabolic profiles facilitate biosynthesis, as compared to those of nondividing cells of the same sort. Recent studies have elucidated specific molecules that control metabolic changes while cells shift between proliferation and quiescence. Embryonic stem cells, which are rapidly proliferating, tend to have metabolic patterns that are similar to those of nonstem cells in a proliferative state. Moreover, although adult stem cells tend to be quiescent, their metabolic profiles have been reported in multiple organs to more closely resemble those of proliferating than those of nondividing cells in some respects. The findings raise questions about whether there are metabolic profiles that are required for stemness, and whether these profiles relate to the metabolic properties that may be required for quiescence. Here, we review the literature on how metabolism changes upon commitment to proliferation and compare the proliferating and nonproliferating metabolic states of differentiated cells and embryonic and adult stem cells.

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Section: Amino Acid Metabolismmentioning

confidence: 98%

Section: Amino Acid Metabolismmentioning

confidence: 98%

The paradox of metabolism in quiescent stem cells

Coller

2019

FEBS Letters

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“…In turn, glutamine metabolism provides carbon for lipids and glutathione biosynthesis and nitrogen for nucleotide biosynthesis and thus regulates oxidative stress and promotes tumor proliferation (Wise and Thompson, 2010;Le et al, 2012). Proliferation of skeletal stem cells can be regulated through glutamine metabolism (Yu et al, 2019), and the proliferation of intestinal stem cells can be regulated by mitochondrial pyruvate metabolism (Schell et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

Fang

Zhang

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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Graphene consists of two-dimensional sp2-bonded carbon sheets, a single or a few layers thick, which has attracted considerable interest in recent years due to its good conductivity and biocompatibility. Three-dimensional graphene foam (3DG) has been demonstrated to be a robust scaffold for culturing neural stem cells (NSCs) in vitro that not only supports NSCs growth, but also maintains cells in a more active proliferative state than 2D graphene films and ordinary glass. In addition, 3DG can enhance NSCs differentiation into astrocytes and especially neurons. However, the underlying mechanisms behind 3DG's effects are still poorly understood. Metabolism is the fundamental characteristic of life and provides substances for building and powering the cell. Metabolic activity is tightly tied with the proliferation, differentiation, and self-renewal of stem cells. This study focused on the metabolic reconfiguration of stem cells induced by culturing on 3DG. This study established the correlation between metabolic reconfiguration metabolomics with NSCs cell proliferation rate on different scaffold. Several metabolic processes have been uncovered in association with the proliferation change of NSCs. Especially, culturing on 3DG triggered pathways that increased amino acid incorporation and enhanced glucose metabolism. These data suggested a potential association between graphene and pathways involved in Parkinson's disease. Our work provides a very useful starting point for further studies of NSC fate determination on 3DG.

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“…[24][25][26] In immune system, miRNA expression patterns can be used as a biomarker for particular disease states such as cancer or endocrine events. [27,28] Evidence also reported that exosomes can be taken up into neighboring or distant cell types to modulate the function of recipient cells. [29] Therefore, to explore the relationship between macrophage-derived exosomal miRNAs and BMSCs, we co-cultured these two cell types, revealing that exosomal miRNAs from macrophages could be internalized by BMSCs, providing a strong basis for our further research.…”

Section: M2d-exos-derived Mir-5106 Accelerates Fracture Healing In Vivomentioning

confidence: 99%

M2 Macrophagy-derived Exosomal MiRNA-5106 Induces Bone Mesenchymal Stem Cells towards Osteoblastic Fate by Targeting Salt-inducible Kinase 2 and 3

Xiong

Chen

Yan

et al. 2020

Preprint

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Background Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo , and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation. Results We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 ( SIK2 and SIK3 ) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo . Conclusions Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.

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Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells

Cited by 182 publications

References 71 publications

The paradox of metabolism in quiescent stem cells

The paradox of metabolism in quiescent stem cells

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

M2 Macrophagy-derived Exosomal MiRNA-5106 Induces Bone Mesenchymal Stem Cells towards Osteoblastic Fate by Targeting Salt-inducible Kinase 2 and 3

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