The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection

Buganim, Yosef; Markoulaki, Styliani; Wietmarschen, Niek van; Hoke, Heather A.; Wu, Tao; Ganz, Kibibi; Akhtar-Zaidi, Batool; He, Yiping; Abraham, Brian J.; Porubský, David; Kulenkampff, Elisabeth; Faddah, Dina A.; Shi, Linqi; Gao, Qing; Sarkar, Sovan; Cohen, Malkiel A.; Goldmann, Johanna; Nery, Joseph R.; Schultz, Matthew D.; Ecker, Joseph R.; Xiao, Andrew; Young, Richard A.; Lansdorp, Peter M.; Jaenisch, Rudolf

doi:10.1016/j.stem.2014.07.003

Cited by 148 publications

(146 citation statements)

References 62 publications

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“…It has been shown that virus-mediated reprogramming of bovine somatic cells required the addition of ectopic NANOG cDNA to the Oct4, Klf4, Sox2, and c-Myc (OKSM) factors for successful epigenetic reprogramming (Sumer et al, 2011). These data are in accordance with a recent study in the mouse (Buganim et al, 2014) showing that the quality of murine iPSC lines correlated positively with the number of reprogramming factors used. The biPS-1 cell line in the present experiments was established with the aid of the PB-6F transposon, which contains NANOG and LIN28.…”

Section: Discussionsupporting

confidence: 83%

Derivation and Characterization of Bovine Induced Pluripotent Stem Cells by Transposon-Mediated Reprogramming

Talluri

Kumar

Glage

et al. 2015

Cellular Reprogramming

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Induced pluripotent stem cells (iPSCs) are a seminal breakthrough in stem cell research and are promising tools for advanced regenerative therapies in humans and reproductive biotechnology in farm animals. iPSCs are particularly valuable in species in which authentic embryonic stem cell (ESC) lines are yet not available. Here, we describe a nonviral method for the derivation of bovine iPSCs employing Sleeping Beauty (SB) and piggyBac (PB) transposon systems encoding different combinations of reprogramming factors, each separated by self-cleaving peptide sequences and driven by the chimeric CAGGS promoter. One bovine iPSC line (biPS-1) generated by a PB vector containing six reprogramming genes was analyzed in detail, including morphology, alkaline phosphatase expression, and typical hallmarks of pluripotency, such as expression of pluripotency markers and formation of mature teratomas in immunodeficient mice. Moreover, the biPS-1 line allowed a second round of SB transposon-mediated gene transfer. These results are promising for derivation of germ linecompetent bovine iPSCs and will facilitate genetic modification of the bovine genome.

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Section: Discussionsupporting

confidence: 83%

Derivation and Characterization of Bovine Induced Pluripotent Stem Cells by Transposon-Mediated Reprogramming

Talluri

Kumar

Glage

et al. 2015

Cellular Reprogramming

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“…In fact, this observation appears to support recent reports highlighting the importance of Esrrb in establishing pluripotency and self-renewal independent of Sox2. [34][35][36] Buganim et al 34 reported that combination of Esrrb, Nanog, Sall4 and Lin28 can efficiently support pluripotency with a quality higher than other factor combinations, including Oct4, Sox2, Klf4 and Myc. 34 Interestingly, in addition to Esrrb and Nanog, the expression levels of Lin28 and Sall4 also maintain at a higher expression level in U1 and U2 cells (Figure 6b).…”

Section: Resultsmentioning

confidence: 99%

Ube2s regulates Sox2 stability and mouse ES cell maintenance

et al. 2015

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Sox2 has a critical role in embryonic stem (ES) cell maintenance and differentiation. Interestingly, its activity is highly dosagedependent. Although transcriptional regulation of Sox2 has been extensively studied, the mechanisms orchestrating its degradation remain unclear. In this study, we identified ubiquitin-conjugating enzyme E2S (Ube2s) as a novel effector for Sox2 protein degradation. Ube2s mediates K11-linked polyubiquitin chain formation at the Sox2-K123 residue, thus marking it for proteasome-mediated degradation. Besides its role in fine-tuning the precise level of Sox2, Ube2s reinforces the self-renewing and pluripotent state of ES cells. Importantly, it also represses Sox2-mediated ES cell differentiation toward the neural ectodermal lineage.

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“…By screening diverse factors that are normally expressed in pluripotent stem cells (PSCs), but not fibroblasts, for their ability to convert fibroblasts to pluripotency, the transcription factors Oct3/4, Sox2, Klf4, and c-Myc (O, S, K, and M) were found to trigger endogenous expression of pluripotent factors and be sufficient to reprogram fibroblasts into induced PSCs (iPSCs) (Takahashi and Yamanaka 2006). Although alternative sets of transcription factors for iPSC reprogramming have been reported (e.g., Buganim et al 2014), most studies include Oct3/4 and/or Sox2 (Yu et al 2007;Feng et al 2009;Han et al 2010;Gao et al 2013). How does this set of factors first interact with their target sites to initiate reprogramming?…”

Section: Pioneer Factors In Cell Reprogrammingmentioning

confidence: 99%

Pioneer transcription factors in cell reprogramming

2014

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A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in ''closed'' chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as ''pioneer factors'' to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.Cell fate control represents the most extreme form of gene regulation. Genes specific to the function of a particular type of cell may be antagonistic to the function of another type of cell, so nature has evolved diverse regulatory mechanisms to ensure stable patterns of gene activation and repression. In prokaryotes, self-sustaining regulatory networks of transcription factors bound to DNA can be sufficient to regulate gene activation and repression (Ptashne 2011). In eukaryotes, ;200-base-pair (bp) segments of the genome are wound nearly twice around an octamer of the four core histones to form nucleosomes, providing steric constraints on how transcription factors can bind DNA (Kornberg and Lorch 1999). As described below, pioneer transcription factors have the special property of being able to overcome such constraints, enabling the factors to engage closed chromatin that is not accessible by other types of transcription factors (Fig. 1). However, further higher-order packaging of nucleosomes into heterochromatin can occlude access to DNA altogether, presenting an additional barrier to cell fate conversion (Fig. 1). This review focuses on the most recent studies of pioneer factors in cell programming and reprogramming, how pioneer factors have special chromatinbinding properties, and facilitators and impediments to chromatin binding. We project that such knowledge will greatly aid future efforts to change the fates of cells at will for research, diagnostic, and therapeutic purposes.

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The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection

Cited by 148 publications

References 62 publications

Derivation and Characterization of Bovine Induced Pluripotent Stem Cells by Transposon-Mediated Reprogramming

Derivation and Characterization of Bovine Induced Pluripotent Stem Cells by Transposon-Mediated Reprogramming

Ube2s regulates Sox2 stability and mouse ES cell maintenance

Pioneer transcription factors in cell reprogramming

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