Abstract
Human pluripotent stem cells provide a versatile platform for regenerative studies, drug testing and disease modeling. That the expression of only four transcription factors, Oct4, Klf4, Sox2 and c-Myc (OKSM), is sufficient for generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells has revolutionized the field and also highlighted the importance of OKSM as targets for genome editing. A number of novel genome-editing systems have been developed recently. In this review, we focus on successful applications of several such systems for generation of iPSCs. In particular, we discuss genome-editing systems based on zinc-finger fusion proteins (ZFs), transcription activator-like effectors (TALEs) and an RNA-guided DNA-specific nuclease, Cas9, derived from the bacterial defense system against viruses that utilizes clustered regularly interspaced short palindromic repeats (CRISPR).
Highlights
The emergence of genome-editing technologies over the past several years has flourished the investigation of human cellular disease models
Irrespective of the exact mechanism, these results indicate that Kruppel-associated Box (KRAB)–zinc-finger proteins (ZFs) can function as an activator of silenced genes in specific chromatin context
The dead Cas9 nuclease (dCas9)-p300 histone acetyltransferase (HAT) protein targeted by a pool of guide RNA (gRNA) to the PE of Oct[4] gene 30-fold more potently activated transcription compared with dCas9-VP64
Summary
One downside of the iPSCs generation process is its low efficacy. In this respect, what will happen when the precision of genome editing systems is combined with the power of small molecule inhibitors that reverse the epigenetic state of differentiated cells?.
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