Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway

Chen, Mengfei; Zhang, He; Wu, Jie; Xu, Liang; Di, Xu; Sun, Jian; He, Yizhu; Zhou, Xin; Wang, Zhaojing; Wu, Lifang; Xu, Shao‐Kun; Jiang, Shu; Zhou, Xiangjun; Hoffman, Andrew R.; Hu, Xiang; Hu, Ji-Fan; Li, Tao

doi:10.1016/j.biomaterials.2012.04.001

Cited by 36 publications

(51 citation statements)

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“…The initiation phase is also characterised by a metabolic switch from oxidative phosphorylation to glycolysis [65] that occurs around 7 d after induction of reprogramming [66] and involves phosphatidylinositol-3-kinase (PI3K)/AKT signalling [53,67] . For example, Chen et al [67] have demonstrated that the PI3K/AKT pathway was activated during reprogramming in parallel with the upregulation of glycolytic gene expression, showing specifically that AKT activated 2 key glycolytic regulators, AS1060 and PFKB2.…”

mentioning

confidence: 99%

“…For example, Chen et al [67] have demonstrated that the PI3K/AKT pathway was activated during reprogramming in parallel with the upregulation of glycolytic gene expression, showing specifically that AKT activated 2 key glycolytic regulators, AS1060 and PFKB2. Zhu et al [53] have also shown that PS48, an activator of the PI3K/AKT pathway, is able to enhance reprogramming by upregulating glycolytic genes.…”

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confidence: 99%

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Cell signalling pathways underlying induced pluripotent stem cell reprogramming

Hawkins

Joy

McKay

2014

WJSC

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Induced pluripotent stem (iPS) cells, somatic cells reprogrammed to the pluripotent state by forced expression of defined factors, represent a uniquely valuable resource for research and regenerative medicine. However, this methodology remains inefficient due to incomplete mechanistic understanding of the reprogramming process. In recent years, various groups have endeavoured to interrogate the cell signalling that governs the reprogramming process, including LIF/STAT3, BMP, PI3K, FGF2, Wnt, TGFβ and MAPK pathways, with the aim of increasing our understanding and identifying new mechanisms of improving safety, reproducibility and efficiency. This has led to a unified model of reprogramming that consists of 3 stages: initiation, maturation and stabilisation. Initiation of reprogramming occurs in almost all cells that receive the reprogramming transgenes; most commonly Oct4, Sox2, Klf4 and cMyc , and involves a phenotypic mesenchymal-to-epithelial transition. The initiation stage is also characterised by increased proliferation and a metabolic switch from oxidative phosphorylation to glycolysis. The maturation stage is considered the major bottleneck within the process, resulting in very few "stabilisation competent" cells progressing to the final stabilisation phase. To reach this stage in both mouse and human cells, pre-iPS cells must activate endogenous expression of the core circuitry of pluripotency, comprising Oct4, Sox2, and Nanog , and thus reach a state of transgene independence. By the stabilisation stage, iPS cells generally use the same signalling networks that govern pluripotency in embryonic stem cells. These pathways differ between mouse and human cells although recent work has demonstrated that this is context dependent. As iPS cell generation technologies move forward, tools are being developed to interrogate the process in more detail, thus allowing a greater understanding of this intriguing biological phenomenon.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Pluripotency; Reprogramming; Induced pluripotent stem; Cell signalling; Embryonic stem Core tip: Induced pluripotent stem (iPS) cells present great promise, both to research and to medicine. However, we know very little regarding the mechanisms that occur throughout the iPS cell reprogramming process and thus the process remains inefficient. In this review, we discuss the 3 stages of reprogramming, initiation, maturation and stabilisation, and clarify the signalling pathways underlying each phase. We draw together the current knowledge to propose a model for the interactions between the key pathways in iPS cell reprogramming with the aim of illuminating this complex yet fascinating process.Hawkins K, Joy S, McKay T. Cell signalling pathways underlying induced pluripotent stem cell reprogramming. World J Stem Cells

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confidence: 99%

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confidence: 99%

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

Hawkins

Joy

McKay

2014

WJSC

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“…PI3K/Akt signaling activation was identified in the initiation phase, being involved in the metabolic switch from oxidative phosphorylation to glycolysis by activation of glycolytic regulators AS1060 and PFKB2 (Chen et al, 2012;Hawkins et al, 2014). Zhu et al demonstrated that Akt activation is capable of increasing reprogramming by upregulation of glycolytic genes (Zhu et al, 2010).…”

Section: Cell Signaling Pathway Modulation Promotes Somatic Cell Reprmentioning

confidence: 99%

Current status of stem cell therapy: opportunities and limitations

Rusu¹,

Necula²,

Neagu³

et al. 2016

Turk J Biol

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Over recent years stem cells have stood out as a promising tool for regenerative medicine, providing alternative therapeutic solutions for a large number of diseases. Many clinical trials using stem cells or induced pluripotent stem cells are focused on the repair and regeneration of various tissues and organs in degenerative diseases, whose current treatment only succeeds in slowing down the progression of the disease. Although the preliminary results are interesting, further studies are required in order to evaluate the safety and benefits of stem cell therapy, considering the teratoma development and ethical considerations in embryonic stem cell cases or reprogramming-induced somatic mutations and epigenetic defects. This review summarizes several current clinical and nonclinical data on the use of embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells in various diseases.

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“…To validate the multipotency of the isolated hUCMSCs, differentiation to adipogenic and osteogenic lineages were performed as described previously [25,32]. After 3 weeks of induction, cells were stained with the oil red O or alizarin red to detect the presence of neutral lipid vacuoles in differentiated adipocytes or calcium deposition in osteocytes, respectively.…”

Section: Adipogenic and Osteogenic Differentiationmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

Li¹,

Ju²,

Zhou³

et al. 2015

Stud Stem Cells Res Ther

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Despite considerable advances in the treatment for systemic lupus erythematosus (SLE), there is still an unmet need to develop novel therapeutic approaches with improved efficacy and lower side effects. Here we explore human umbilical cord-derived mesenchymal stem cells (hUCMSCs) as a promising treatment for SLE induced by concanavalin A-activated spleno-lymphocyte in BALB/c mice. The isolated hUCMSCs, carrying specific MSC cell surface markers (CD105, CD73 and CD90), exhibited the potential to differentiate into osteogenic and adipogenic lineages. In mice with SLE, transplantation of hUCMSCs improved disease symptoms by decreasing the levels of serum autoantibody (antidsDNA and anti-nuclear) and cytokines (TNF-α and IFN-γ). The cell therapy significantly alleviated renal lesions by lowering serum urea nitrogen, creatine and uric acid, and increasing albumin. Using immunohistochemical staining, we found that that hUCMSCs decreased endocapillary hypercellularity, glomerular degeneration, and complement C3 immune complex deposition in the kidney. Mechanically, the therapy with hUCMSCs decreased CD4+/CD8+ cell ratio in animals. These data suggest that hUCMSCs may modulate autoimmunity in SLE mice by rebalancing CD4+/CD8+ cell population. Transplantation of hUCMSCs may be explored as a promising alternative approach in the treatment of human lupus.

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Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway

Cited by 36 publications

References 51 publications

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

Current status of stem cell therapy: opportunities and limitations

Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

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