Biomedical Engineering Reference
In-Depth Information
Molecular Regulation of the State of Embryonic
Stem Cells
Yuko Fujiwara and Stuart H. Orkin
Abstract Pluripotency is a defining feature of embryonic stem cells (ESCs). A
mechanistic understanding of pluripotency should shed light on fundamental
aspects of development. In this chapter, we review the extrinsic factors, protein,
and gene regulatory networks and epigenetics of ESCs. With the availability of
human ESCs and the capacity to reprogram somatic cells to a pluripotent state,
we hope that a comprehensive description of the control of pluripotency in
ESCs will contribute to the use of these cells in regenerative medicine.
Contents
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33
2 Extrinsic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
35
3
''Core'' Transcription Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
39
4 Pluripotency Genomics and Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
42
5 Extended Transcriptional Network: ChIP-ChIP . . . . . . . . . . . . . . . . . . . . . . . . . . .
44
6 Epigenetics in ESCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
48
7 State of ESCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1 Introduction
It has been nearly three decades since mouse ESCs (embryonic stem cells) were
first isolated from the inner cell mass (ICM) of preimplantation blastocysts. The
generation of hESCs (human embryonic stem cells) and recent success in
reprogramming of adult somatic cells to hiPS (human-induced pluripotent
stem cells) has brought extraordinary attention to the stem cell field. Mouse
(m)ESCs have been used for gene knockout studies for about 20 years. In spite
S.H. Orkin (*)
Department of Pediatric Oncology, Children's Hospital Boston, Dana Faber Cancer
Institute, Harvard Medical School, Howard Hughes Medical Institute, Boston,
Maryland, USA
