Review

Citation: Cell Death and Disease (2015) 6, e1831; doi:10.1038/cddis.2015.167
Published online 23 July 2015

Genome-editing tools for stem cell biology
Open

E A Vasileva1, O U Shuvalov1, A V Garabadgiu2, G Melino2,3 and N A Barlev1,2

  1. 1Institute of Cytology, RAS, Saint-Petersburg, Russia
  2. 2Technological University, Saint-Petersburg, Russia
  3. 3MRC Toxicology Unit, Leicester, UK

Correspondence: NA Barlev, Institute of Cytology, RAS, Saint-Petersburg, Russia. Tel: +79117022188; E-mail: nick.a.barlev@gmail.com

Received 26 March 2015; Revised 15 May 2015; Accepted 18 May 2015

Edited by G Kroemer

Top

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).

Abbreviations:

CR, conservative region; CRISPR, clustered regularly interspaced short palindromic repeat; dCas9, dead Cas9 nuclease; DE, distal enhancer; ESC, embryonic stem cell; FD, functional domain; gRNA, guide RNA; iPSC, induced pluripotent stem cell; LITE, light-inducible transcriptional effector; OKSM, Oct4, Klf4, Sox2 and c-Myc; PAM, protospacer adjacent motif; PE, proximal enhancer; PSC, pluripotent stem cell; RVD, repeat variable di-residue; sgRNA, single-guide RNA; SL1-3, stem loop 1-3; TALE, transcription activator-like effector; TALEN, transcription activator-like effector nuclease; TF, transcription factor; ZF, zinc-finger protein; ZFN, zinc-finger nuclease