Suppression of induced pluripotent stem cell generation by the p53–p21 pathway

  title={Suppression of induced pluripotent stem cell generation by the p53–p21 pathway},
  author={Hyenjong Hong and Kazutoshi Takahashi and Tomoko Ichisaka and Takashi Aoi and Osami Kanagawa and Masato Nakagawa and Keisuke Okita and Shinya Yamanaka},
Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined… 

The p53–PUMA axis suppresses iPSC generation

It is shown that depletion of the pro-apoptotic factor PUMA, acting downstream of p53, increases reprogramming efficiency, providing new insights into the roles of p52 and p53 in reprograming.

Generation of mouse-induced pluripotent stem cells with plasmid vectors

An alternative method to generate iPS cells from mouse embryonic fibroblasts (MEFs) by continual transfection of plasmid vectors is described, which reduces the safety concern for iPS cell generation and application, and provides a source of cells for the investigation of the mechanisms underlying reprogramming and pluripotency.

Context‐Dependent Enhancement of Induced Pluripotent Stem Cell Reprogramming by Silencing Puma

This work discovered that the majority of the p53 activation occurred through early reprogramming‐induced DNA damage with the activated expression of the apoptotic inducer Puma and the cell cycle inhibitor p21.

Stem cells: The great iPS barrier

Five new studies suggest that depletion of p53, ARF, p16INK4A or p21 can increase the kinetics and efficiency of iPS cell generation and it will be important to determine how the p16inks4A and ARF–p53 tumour suppressor pathways can be silenced to allow the efficient production of i PS cells without increasing the possibility of malignant transformation.

Induced pluripotent stem cells: opportunities and challenges

  • K. OkitaS. Yamanaka
  • Biology
    Philosophical Transactions of the Royal Society B: Biological Sciences
  • 2011
The current knowledge of iPS generation is summarized, the need for improvement of the reprogramming procedure not only in quantity but also in quality is suggested, and future reprograming methods for medical application are discussed.

Direct generation of induced pluripotent stem cells from human nonmobilized blood.

Generation of iPSCs from MNCs of nonmobilized PB, with its relative efficiency and ease of harvesting, could enable the therapeutic use of patient-specific pluripotent stem cells.

Multiple roles of p53-related pathways in somatic cell reprogramming and stem cell differentiation.

It is found that little or no p53 activity favors the entire process of somatic cell reprogramming, and the production of iPSCs in culture from normal and cancer cells, although different from each other in several ways, both responded to the inhibition of reprograming by the p53 protein.

Inhibition of PTEN Tumor Suppressor Promotes the Generation of Induced Pluripotent Stem Cells.

It is shown that activation of the PI3K pathway by the Pten inhibitor, dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate, improves the efficiency of germline-competent iPSC derivation from mouse somatic cells, providing a new approach for efficient generation of iPSCs.

Role of tumor suppressor genes in the cancer-associated reprogramming of human induced pluripotent stem cells

The critical role of tumor suppressor genes in the evaluation of the tumorigenicity of human cancer cell-derived pluripotent stem cells is discussed, and how to overcome their tumorigenic properties for application in stem cell therapy in the field of regenerative medicine is described.

Title Induced pluripotent stem cells : opportunities and challenges

The current knowledge of iPS generation is summarized and future reprogramming methods for medical application are discussed, suggesting the need for improvement of the reprograming procedure not only in quantity but also in quality.



Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors

The production of virus-free iPS cells, albeit from embryonic fibroblasts, addresses a critical safety concern for potential use of i PS cells in regenerative medicine.

Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts

A modified protocol for the generation of iPS cells that does not require the Myc retrovirus is described and, with this protocol, significantly fewer non-iPS background cells are obtained, and theiPS cells generated were consistently of high quality.

Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells

Genetic lineage tracings suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.

Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells

Somatic cell nuclear transfer allows trans-acting factors present in the mammalian oocyte to reprogram somatic cell nuclei to an undifferentiated state. We show that four factors (OCT4, SOX2, NANOG,

Tissue-specific inactivation of p53 tumor suppression in the mouse.

Inactivation of endogenous p53, which is shown to be complexed with p53DD, results in a reduction in apoptosis and acceleration of tumorigenesis, establishing a mechanism for tissue-specific knock out of p53 function in vivo.

Strategies and new developments in the generation of pluripotent stem cells.

This review discusses the different strategies that have been used to induce the conversion of a differentiated cell into an embryonic pluripotent state, including nuclear transfer, cellular fusion, culture-induced and defined factors reprogramming.