MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming

Prieto, Javier; Seo, Arnold Y.; León, Marian; Santacatterina, Fulvio; Torresano, Laura; Palomino‐Schätzlein, Martina; Giménez, Karen; Vallet-Sánchez, Azahara; Ponsoda, Xavier; Pineda‐Lucena, Antonio; Cuezva, José M.; Lippincott‐Schwartz, Jennifer; Torres, Josema

doi:10.1016/j.stemcr.2018.10.018

Cited by 34 publications

(41 citation statements)

References 39 publications

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“…However, fatty acid oxidation (FAO) was unchanged in IAV-infected DC concomitant to a decrease in intracellular free fatty acids (Fig 2E & 2F). Together, the increase in glycolysis and glutaminolyisis with decreased pyruvate utilization in the TCA cycle is consistent with the two major metabolic pathways becoming uncoupled to maintain ATP production while increasing metabolic plasticity [31][32][33][34][35][36].…”

Section: Restructure Metabolic Flux After Iav Infectionsupporting

confidence: 55%

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

et al. 2020

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Infection with the influenza virus triggers an innate immune response that initiates the adaptive response to halt viral replication and spread. However, the metabolic response fueling the molecular mechanisms underlying changes in innate immune cell homeostasis remain undefined. Although influenza increases parasitized cell metabolism, it does not productively replicate in dendritic cells. To dissect these mechanisms, we compared the metabolism of dendritic cells to that of those infected with active and inactive influenza A virus and those treated with toll-like receptor agonists. Using quantitative mass spectrometry, pulse chase substrate utilization assays and metabolic flux measurements, we found global metabolic changes in dendritic cells 17 hours post infection, including significant changes in carbon commitment via glycolysis and glutaminolysis, as well as mitochondrial respiration. Influenza infection of dendritic cells led to a metabolic phenotype distinct from that induced by TLR agonists, with significant resilience in terms of metabolic plasticity. We identified c-Myc as one transcription factor modulating this response. Restriction of c-Myc activity or mitochondrial substrates significantly changed the immune functions of dendritic cells, such as reducing motility and T cell activation. Transcriptome analysis of inflammatory dendritic cells isolated following influenza infection showed similar metabolic reprogramming occurs in vivo. Thus, early in the infection process, dendritic cells respond with global metabolic restructuring, that is present in inflammatory lung dendritic cells after infection, and this is important for effector function. These findings suggest metabolic switching in dendritic cells plays a vital role in initiating the immune response to influenza infection.

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Section: Restructure Metabolic Flux After Iav Infectionsupporting

confidence: 55%

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

et al. 2020

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“…In contrast, the inhibition of ERR expression fails to induce successful reprogramming [51]. Moreover, the fact that c-MYC can significantly upregulate the expression levels of glycolysis-and OXPHOS-related enzymes demonstrates the deep involvement of c-MYC in metabolic shift at the early stage of reprogramming [52]. Considering that c-MYC, together with HIF1, regulates metabolic remodeling in cancer cells under hypoxic conditions [53,54], c-MYC and HIF1 may cooperate to induce metabolic shift during iPSC reprogramming as well.…”

Section: Metabolic Shift During Reprogramming To Ipscsmentioning

confidence: 99%

“…Mitochondrial mass is also decreased by iPSC reprogramming [12]. Forced expression of c-MYC affects mitochondrial morphology, which changes from tubular to fragmented, accompanied by upregulation of the mitochondrial fission regulator, dynamin-related protein 1 (DRP1), and elevation of the mitochondrial membrane potential as a mitochondrial function indicator [52]. As for the effect of modulation of mitochondrial dynamics, DRP1 inhibition reduces reprogramming efficiency [57,58].…”

Section: Metabolic Shift During Reprogramming To Ipscsmentioning

confidence: 99%

Metabolic remodeling during somatic cell reprogramming to induced pluripotent stem cells: involvement of hypoxia-inducible factor 1

et al. 2020

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Induced pluripotent stem cells (iPSCs) were first established from differentiated somatic cells by gene introduction of key transcription factors, OCT4, SOX2, KLF4, and c-MYC, over a decade ago. Although iPSCs can be applicable for regenerative medicine, disease modeling and drug screening, several issues associated with the utilization of iPSCs such as low reprogramming efficiency and the risk of tumorigenesis, still need to be resolved. In addition, the molecular mechanisms involved in the somatic cell reprogramming to pluripotency are yet to be elucidated. Compared with their somatic counterparts, pluripotent stem cells, including embryonic stem cells and iPSCs, exhibit a high rate of glycolysis akin to aerobic glycolysis in cancer cells. This is known as the Warburg effect and is essential for maintaining stem cell properties. This unique glycolytic metabolism in iPSCs can provide energy and drive the pentose phosphate pathway, which is the preferred pathway for rapid cell proliferation. During reprogramming, somatic cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis trigged by a transient OXPHOS burst, resulting in the initiation and progression of reprogramming to iPSCs. Metabolic intermediates and mitochondrial functions are also involved in the epigenetic modification necessary for the process of iPSC reprogramming. Among the key regulatory molecules that have been reported to be involved in metabolic shift so far, hypoxia-inducible factor 1 (HIF1) controls the transcription of many target genes to initiate metabolic changes in the early stage and maintains glycolytic metabolism in the later phase of reprogramming. This review summarizes the current understanding of the unique metabolism of pluripotent stem cells and the metabolic shift during reprogramming, and details the relevance of HIF1 in the metabolic shift.

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“…Moreover, c-Myc and either of the other factors can bind simultaneously to specific genetic elements, resulting in chromatin decondensation followed by enhanced gene expression [39]. The reprogramming transcription factors also induce a switch in the metabolic network of the cells, which enhances the efficiency of cellular reprogramming [40,41].…”

Section: Cellular Reprogramming and Ips Cellsmentioning

confidence: 99%

Cellular Reprogramming—A Model for Melanoma Cellular Plasticity

Granados

Poelchen

Novak

et al. 2020

IJMS

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Cellular plasticity of cancer cells is often associated with phenotypic heterogeneity and drug resistance and thus remains a major challenge for the treatment of melanoma and other types of cancer. Melanoma cells have the capacity to switch their phenotype during tumor progression, from a proliferative and differentiated phenotype to a more invasive and dedifferentiated phenotype. However, the molecular mechanisms driving this phenotype switch are not yet fully understood. Considering that cellular heterogeneity within the tumor contributes to the high plasticity typically observed in melanoma, it is crucial to generate suitable models to investigate this phenomenon in detail. Here, we discuss the use of complete and partial reprogramming into induced pluripotent cancer (iPC) cells as a tool to obtain new insights into melanoma cellular plasticity. We consider this a relevant topic due to the high plasticity of melanoma cells and its association with a strong resistance to standard anticancer treatments.

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MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming

Cited by 34 publications

References 39 publications

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

Dynamic metabolic reprogramming in dendritic cells: An early response to influenza infection that is essential for effector function

Metabolic remodeling during somatic cell reprogramming to induced pluripotent stem cells: involvement of hypoxia-inducible factor 1

Cellular Reprogramming—A Model for Melanoma Cellular Plasticity

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