An improved method for the derivation of high quality iPSCs in the absence of c-Myc

Habib, Omer; Habib, Gizem; Choi, Hyun Woo; Hong, Ki-Sung; Tae, Jeong; Moon, Sung-Hwan; Chung, Hyung-Min

doi:10.1016/j.yexcr.2013.09.014

Cited by 12 publications

(9 citation statements)

References 54 publications

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“…Klf4 only plays a role in the early stage of the cellular reprogramming [56], and cMyc as an oncogene is not essential for the generation and maintenance of the iPSCs [57]. High-level expression of cMyc has negative effect on the pluripotency of iPSCs [58]. Low-level expression of cMyc suggested that the biPSCs were impossible to be cancerous cells.…”

Section: Discussionmentioning

confidence: 99%

Generation and characterization of bat-induced pluripotent stem cells

2014

Theriogenology

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Induced pluripotent stem cells (iPSCs) were first generated from mouse embryonic fibroblasts in the year 2006. These cells resemble the typical morphology of embryonic stem cells, express pluripotency markers, and are able to transmit through germlines. To date, iPSCs of many species have been generated, whereas generation of bat iPSCs (biPSCs) has not been reported. To facilitate in-depth study of bats at the molecular and cellular levels, we describe the successful derivation of biPSCs with a piggyBac (PB) vector that contains eight reprogramming factors Oct4, Sox2, Klf4, Nanog, cMyc, Lin28, Nr5a2, and miR302/367. These biPSCs were cultured in media containing leukemia inhibitory factor and three small molecule inhibitors (CHIR99021, PD0325901, and A8301). They retained normal karyotype, displayed alkaline phosphatase activity, and expressed pluripotency markers Oct4, Sox2, Nanog, TBX3, and TRA-1-60. They could differentiate in vitro to form embryoid bodies and in vivo to form teratomas that contained tissue cells of all three germ layers. Generation of biPSCs will facilitate future studies on the mechanisms of antiviral immunity and longevity of bats at the cellular level.

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Section: Discussionmentioning

confidence: 99%

Generation and characterization of bat-induced pluripotent stem cells

2014

Theriogenology

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“…Abnormal epigenetic modifications can ultimately affect the pluripotency of iPSCs; the disrupted methylation could not be recovered by optimizing culture conditions or by subcloning iPSCs. In addition, reactivation of C-MYC might result in tumor formation, but the absence of C-MYC drastically reduced the reprogramming efficiency and resulted in subtle abnormal epigenetic modifications [ 114 ]. Although the genomic integrity of iPSCs has limited their clinical applications, numerous reprogramming strategies were developed to minimize the disturbance of the iPSC genome.…”

Section: The Potential Applications Of Ipsc-derived Hlcsmentioning

confidence: 99%

Two Effective Routes for Removing Lineage Restriction Roadblocks: From Somatic Cells to Hepatocytes

2015

IJMS

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The conversion of somatic cells to hepatocytes has fundamentally re-shaped traditional concepts regarding the limited resources for hepatocyte therapy. With the various induced pluripotent stem cell (iPSC) generation routes, most somatic cells can be effectively directed to functional stem cells, and this strategy will supply enough pluripotent material to generate promising functional hepatocytes. However, the major challenges and potential applications of reprogrammed hepatocytes remain under investigation. In this review, we provide a summary of two effective routes including direct reprogramming and indirect reprogramming from somatic cells to hepatocytes and the general potential applications of the resulting hepatocytes. Through these approaches, we are striving toward the goal of achieving a robust, mature source of clinically relevant lineages.

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“…This simple elimination of c-Myc in iPSCs eliminated the development of tumors during the study period, albeit with a decreasing reprogramming efficiency [35]. This low-efficiency issue, however, was minimized by using a modified low-serum culture protocol to obtain high quality iPSCs [36]. Poly (ADP-ribose) polymerase-1 was also found to act as a replacement for c-Myc or Klf4 and enhanced the efficiency of iPSC generation [37].…”

Section: Cell Transfectionmentioning

confidence: 99%

Myocardial Reprogramming Medicine: The Development, Application, and Challenge of Induced Pluripotent Stem Cells

Wang

2014

New Journal of Science

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Induced pluripotent stem cells (iPSCs) can be generated by reprogramming of adult/somatic cells. The somatic cell reprogramming technology offers a promising strategy for patient-specific cardiac regenerative medicine, disease modeling, and drug discovery. iPSCs are an ideal potential option for an autologous cell source, as compared to other stem/progenitor cells, because they can be propagated indefinitely and are able to generate a large number of functional cardiovascular cells. However, there are concerns about the specificity, efficiency, immunogenicity, and safety of iPSCs which are major challenges in current translational studies. In order to bring iPSC technology closer to clinical use, fundamental changes in this technique are required to ensure that therapeutic progenies are functional and nontumorigenic. It is therefore critical to understand and investigate the biology, genetic, and epigenetic mechanisms of iPSCs generation and differentiation. In this spotlight paper the discovery, history, and relative mechanisms of iPSC generation are summarized. The current technological improvements and potential applications are highlighted along with the important challenges and perspectives. Finally, emerging technologies are presented in which improvements to iPSC generation and differentiation approaches might warrant further investigation, such as integration-free approaches, direct reprogramming, and the development of iPSC banking.

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An improved method for the derivation of high quality iPSCs in the absence of c-Myc

Cited by 12 publications

References 54 publications

Generation and characterization of bat-induced pluripotent stem cells

Generation and characterization of bat-induced pluripotent stem cells

Two Effective Routes for Removing Lineage Restriction Roadblocks: From Somatic Cells to Hepatocytes

Myocardial Reprogramming Medicine: The Development, Application, and Challenge of Induced Pluripotent Stem Cells

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