Reprogramming and the Pluripotent Stem Cell Cycle - Current Topics in Developmental Biology - page 220

CHAPTER SEVEN

Reprogramming and the
Pluripotent Stem Cell Cycle

Tomomi Tsubouchi * , Amanda G. Fisher † ,1
* MRC Genome Damage and Stability Centre, University of Sussex, Falmer, United Kingdom
† MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
1 Corresponding author: e-mail address: [e-mail]

Contents
1. Introduction 223

2. The Embryonic Stem Cell Cycle 225

3. Methods for Restoring Pluripotency 227

4. Critical Stages and Events in Epigenetic Reprogramming 231

5. DNA Synthesis and Chromatin Remodeling in Reprogramming 233

6. Concluding Remarks 235

Acknowledgments 235

References 236

Abstract
Embryonic stem cells (ESCs) can self renew and retain the potential to differentiate into
each of the cell types within the body. During experimental reprogramming, many of
the features of ESCs can be acquired by differentiated target cells. One of these is the
unusual cell division cycle that characterizes ESCs in which the Gap (G) phases are short
and DNA Synthesis (S) phase predominates. Growing evidence has suggested that this
atypical cell-cycle structure may be important for maintaining pluripotency and for
enhancing pluripotent conversion. Here, we review current knowledge of cell-cycle reg-
ulation in ESCs and outline how this unique cell-cycle structure might contribute to
successful reprogramming.

1. INTRODUCTION

The isolation of embryonic stem cells (ESCs) from the inner cell mass
of mouse ( Evans & Kaufman, 1981; Martin, 1981 ) and human blastocysts
( Thomson et al., 1998 ) has revolutionized modern experimental genetics
and our understanding of pluripotency. ESCs can differentiate into all
the cell types within the body (i.e. they are pluripotent) and can divide