Energy Metabolism Plays a Critical Role in Stem Cell Maintenance and Differentiation

Hu, Chenxia; Fan, Linxiao; Cen, Panpan; Chen, Ermei; Jiang, Zhengyi

doi:10.3390/ijms17020253

Cited by 103 publications

(75 citation statements)

References 136 publications

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“…Numerous populations of multipotent stem cells undergo aerobic glycolysis in the stem cell niche to sustain their energy demands [10]. Examples include hematopoietic stem cells in the bone marrow [11], intestinal crypt stem cells [12] and hair follicle stem cells [13].…”

Section: Introductionmentioning

confidence: 99%

“…During both osteogenic and adipogenic differentiations of MSCs, HIF1α is down-regulated, resulting in a loss of aerobic glycolysis accompanied by increased mitogenesis and elevated OxPhos [20,22]. Increased levels of reactive oxygen species, predominately produced by the ETC, induce adipogenic differentiation within MSCs which can be blocked by antioxidant treatment [10,23]. These observations provide a link between differentiation status and metabolic activity.…”

Section: Introductionmentioning

confidence: 99%

“…These observations provide a link between differentiation status and metabolic activity. ROS scavengers such as catalase and superoxide dismutase are down-regulated as MSCs transition to an adipose cell fate [10,22]. However, ROS generation inhibits osteogenic differentiations through the canonical Wnt signaling pathway [17,24].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

Cliff

Dalton

2017

Current Opinion in Genetics & Development

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Cell fate decisions are closely linked to changes in metabolic activity. Over recent years this connection has been implicated in mechanisms underpinning embryonic development, reprogramming and disease pathogenesis. In addition to being important for supporting the energy demands of different cell types, metabolic switching from aerobic glycolysis to oxidative phosphorylation plays a critical role in controlling biosynthetic processes, intracellular redox state, epigenetic status and reactive oxygen species levels. These processes extend beyond ATP synthesis by impacting cell proliferation, differentiation, enzymatic activity, ageing and genomic integrity. This review will focus on how metabolic switching impacts decisions made by multipotent cells and discusses mechanisms by which this occurs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

Cliff

Dalton

2017

Current Opinion in Genetics & Development

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“…While our Sox9 study portrayed how activation of hepatic progenitor cell markers endows a stemness phenotype in HCC, our current study on GATA6 illustrates how downregulation of deterministic transcription factors could revert tumor cells to stem cell‐like phenotype in terms of functions and metabolic signature. The latter, as a matter of fact, recapitulates that of embryonic undifferentiated stem cells which shift from glycolysis to oxidative phosphorylation during the process of differentiation to somatic cells . In embryonal stem cells, multiple glycolytic enzymes were shown to be targets of pluripotent factors Nanog, Oct4 and Sox2 by ChIP‐seq analysis .…”

Section: Discussionmentioning

confidence: 91%

Deregulated GATA6 modulates stem cell‐like properties and metabolic phenotype in hepatocellular carcinoma

Tan

Leung

Chan

et al. 2019

Intl Journal of Cancer

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Accumulating evidence illustrates the significance of cell plasticity in the molecular biology of liver cancer. Reprogramming of mature parenchymal cells to a less differentiated state by key molecular targets contributes to the pathogenesis of hepatocellular carcinoma (HCC). Hereby, we investigated the role of GATA6, a transcription factor implicated in hepatocyte lineage specification, in HCC. Our results demonstrated a lower expression of GATA6 in HCC tissues compared to the corresponding nontumoral liver tissues. Moreover, GATA6 underexpression, as observed in about 50% cases in our clinical cohort, was associated with a poorer degree of tumor cell differentiation and worse disease‐free survival outcome. In vitro, silencing of GATA6 in HCC cells augmented cell migration and invasion abilities of HCC cells by activating epithelial–mesenchymal transition. Self‐renewal was also enhanced in vitro. Consistently, in vivo tumorigenicity and self‐renewal was promoted upon GATA6 knockdown. Notably, suppression of GATA6 converts HCC cells to a metabolic phenotype recapitulating stem‐cell state. Expression of glycolytic markers was elevated in GATA6‐knockdown clones accompanied by increased glucose uptake; while overexpression of GATA6 resulted in opposite effects. Further to this, we identified that GATA6 bound to the promoter region of PKM gene and regulated PKM2 transcription. Taken together, downregulation of GATA6 directs HCC cells to glycolytic metabolism and fosters tumorigenicity, self‐renewal and metastasis. GATA6 is a transcriptional regulator and a genetic switch that converts the phenotypic reprogramming of HCC cells. It is a potential prognostic biomarker and therapeutic target for liver cancer.

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“…Previous studies have found that metabolism is a key determinant of whether a cell proliferates, differentiates, or remains quiescent [28–30]. A recent study conducted by Lyublinskaya and colleagues found that reactive oxygen species (ROS) are required for MSC to initiate proliferation [31].…”

Section: Discussionmentioning

confidence: 99%

Effects of Poor Maternal Nutrition during Gestation on Bone Development and Mesenchymal Stem Cell Activity in Offspring

et al. 2016

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Poor maternal nutrition impairs overall growth and development of offspring. These changes can significantly impact the general health and production efficiency of offspring. Specifically, poor maternal nutrition is known to reduce growth of bone and muscle, and increase adipose tissue. Mesenchymal stem cells (MSC) are multipotent stem cells which contribute to development of these tissues and are responsive to changes in the maternal environment. The main objective was to evaluate the effects of poor maternal nutirtion during gestation on bone and MSC function in offspring. Thirty-six ewes were fed 100%, 60%, or 140% of energy requirements [NRC, 1985] beginning at day 31 ± 1.3 of gestation. Lambs from ewes fed 100% (CON), 60% (RES) and 140% (OVER) were euthanized within 24 hours of birth (1 day; n = 18) or at 3 months of age (n = 15) and bone and MSC samples were collected. Dual X-ray absorptiometry was performed on bones obtained from day 1 and 3 months. Proliferation, differentiation, and metabolic activity were determined in the MSC isolated from lambs at day 1. Data were analyzed using mixed procedure in SAS. Maternal diet negatively affected offspring MSC by reducing proliferation 50% and reducing mitochondrial metabolic activity. Maternal diet did not alter MSC glycolytic activity or differentiation in culture. Maternal diet tended to decrease expression of P2Y purinoreceptor 1, but did not alter expression of other genes involved in MSC proliferation and differentiation. Maternal diet did not alter bone parameters in offspring. In conclusion, poor maternal diet may alter offspring growth through reduced MSC proliferation and metabolism. Further studies evaluating the potential molecular changes associated with altered proliferation and metabolism in MSC due to poor maternal nutrition are warranted.

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Energy Metabolism Plays a Critical Role in Stem Cell Maintenance and Differentiation

Cited by 103 publications

References 136 publications

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

Deregulated GATA6 modulates stem cell‐like properties and metabolic phenotype in hepatocellular carcinoma

Effects of Poor Maternal Nutrition during Gestation on Bone Development and Mesenchymal Stem Cell Activity in Offspring

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