Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation

Liu, Wenbo; Long, Qi; Chen, Keshi; Li, Shengbiao; Ge, Xiang; Chen, Shen; Liu, Xiyin; Li, Yuxing; Yang, Liang; Dong, Delu; Jiang, Ching-Long; Feng, Zhenhua; Qin, Dajiang

doi:10.1016/j.bbrc.2012.12.148

Cited by 25 publications

(24 citation statements)

References 22 publications

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“…Indeed, cells depleted of Pnpt1 are known to have less mitochondrial biogenesis and activity (Wang et al, 2010a), consistent with our observations. This is also consistent with others' observations of lower mitochondrial biogenesis and activity in pluripotent stem cells (Prigione et al, 2010;Folmes et al, 2011;Liu et al, 2013). As a regulator of mitochondrial homeostasis, we found that Tcl1-PnPase regulates mitochondrial OxPhos, the ATP/AMP ratio, the redox balance, and, thus, the glycolytic flux.…”

Section: Discussionsupporting

confidence: 93%

Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming

et al. 2015

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Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC) reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis of pluripotency biomarkers further show that the Tcl1 oocyte factors improve the quality of reprogramming. Mechanistically, we find that the enhancement effect of Tcl1b1 depends on Akt, one of its putative targets. In contrast, Tcl1 suppresses the mitochondrial polynucleotide phosphorylase (PnPase) to promote reprogramming. Knockdown of PnPase rescues the inhibitory effect from Tcl1 knockdown during reprogramming, whereas PnPase overexpression abrogates the enhancement from Tcl1 overexpression. We further demonstrate that Tcl1 suppresses PnPase's mitochondrial localization to inhibit mitochondrial biogenesis and oxidation phosphorylation, thus remodeling the metabolome. Hence, we identified the Tcl1-PnPase pathway as a critical mitochondrial switch during reprogramming.

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Section: Discussionsupporting

confidence: 93%

Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming

et al. 2015

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“…It has been previously shown that ROS and redox-signaling mechanisms play a key role in cell fate decisions, including neurogenesis (Maryanovich and Gross, 2013;Prozorovski et al, 2015), although the molecular mechanisms mediating these effects are not yet fully understood. In iPSC reprogramming, changes to a more glycolytic metabolism have been shown to govern fate conversion (Liu et al, 2013b), despite the initial oxidative burst mentioned above (Kida et al, 2015). The faster neuronal conversion when excessive oxidation products are successfully controlled is consistent with (1) ROS affecting gene expression, e.g., by altering SIRT activity, a key regulator of neurogenesis, and (2) interfering with metabolic pathways acting upstream of other aspects of fate conversion.…”

Section: Different Modes Of Cell Death and Oxidative Stress Limit Neumentioning

confidence: 95%

Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming

et al. 2016

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Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-wide expression analysis confirmed that treatments promoting neuronal reprogramming elicit an anti-oxidative stress response. Importantly, co-expression of Bcl-2 and anti-oxidative treatments leads to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury in vivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type in vitro and in vivo.

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“…Stem cell populations present within various skeletal tissues are typically in a quiescent state, have limited mitochondrial activity, and meet energy demands through glycolysis . Activation of stem cell populations involves a shift to oxidative phosphorylation .…”

Section: Emerging Areas For Stem Cells and Fracture Repair: What The mentioning

confidence: 99%

The Convergence of Fracture Repair and Stem Cells: Interplay of Genes, Aging, Environmental Factors and Disease

Hadjiargyrou

O’Keefe

2014

Journal of Bone and Mineral Research

110

106

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The complexity of fracture repair makes it an ideal process for studying the interplay between the molecular, cellular, tissue, and organ level events involved in tissue regeneration. Additionally, as fracture repair recapitulates many of the processes that occur during embryonic development, investigations of fracture repair provide insights regarding skeletal embryogenesis. Specifically, inflammation, signaling, gene expression, cellular proliferation and differentiation, osteogenesis, chondrogenesis, angiogenesis, and remodeling represent the complex array of interdependent biological events that occur during fracture repair. Here we review studies of bone regeneration in genetically modified mouse models, during aging, following environmental exposure, and in the setting of disease that provide insights regarding the role of multipotent cells and their regulation during fracture repair. Complementary animal models and ongoing scientific discoveries define an increasing number of molecular and cellular targets to reduce the morbidity and complications associated with fracture repair. Last, some new and exciting areas of stem cell research such as the contribution of mitochondria function, limb regeneration signaling, and microRNA (miRNA) posttranscriptional regulation are all likely to further contribute to our understanding of fracture repair as an active branch of regenerative medicine.

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Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation

Cited by 25 publications

References 22 publications

Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming

Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming

Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming

The Convergence of Fracture Repair and Stem Cells: Interplay of Genes, Aging, Environmental Factors and Disease

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