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35 - MicroRNAs in embryonic stem cell differentiation and prediction of their targets

from VI - MicroRNAs in stem cell development

Published online by Cambridge University Press:  22 August 2009

By
Yvonne Tay ,
Andrew M. Thomson  and
Bing Lim
Edited by
Krishnarao Appasani
Foreword by
Sidney Altman  and
Victor R. Ambros
Yvonne Tay
Affiliation:
Stem Cell and Developmental Biology Genome Institute of Singapore 60 Biopolis Street, #02-01, Genome Singapore 138672
Andrew M. Thomson
Affiliation:
Stem Cell and Developmental Biology Genome Institute of Singapore 60 Biopolis Street, #02-01, Genome Singapore 138672
Bing Lim
Affiliation:
Stem Cell and Developmental Biology Genome Institute of Singapore 60 Biopolis Street, #02-01, Genome Singapore 138672
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Summary

Introduction

Embryonic stem cells (ESCs) exhibit the capacity for unlimited self-renewal and the ability to differentiate into multiple cell lineages, and are termed pluripotent (Smith, 2001; Czyz et al., 2003). The study of mammalian ESCs may facilitate understanding of early developmental events and contribute to the advance of cell-based regenerative medicine (Loebel at al., 2003). ESCs are isolated from the inner cell mass (ICM) of the pre-implantation embryo (Evans and Kaufman, 1981) and share many properties with pluripotent cells from the ICM (Figure 35.1). These include the expression of key regulators of pluripotency and self-renewal, Oct4, Sox2 and Nanog, and the capacity to differentiate to all cell types of the embryo, including mesoderm, ectoderm and endoderm (Orkin, 2005). Oct4 is activated at the four cell stage of mouse pre-implantation development and is essential for the formation of the ICM (Chew et al., 2005). Increased Oct4 levels in mouse ESCs (mESCs) result in differentiation to primitive endoderm and mesoderm, whereas a reduction leads to differentiation to trophectoderm (Niwa et al., 2000). Co-regulation of genes by Oct4 and Sox2 appears to be essential in maintaining self-renewal of ESCs (Chew et al., 2005). Nanog acts in concert with Oct4 and Sox2, where Nanog overexpression negates the requirement for leukemia-inhibitory factor (LIF)-activated signaling by mESCs for self-renewal (Mitsui et al., 2003). Nanog knockout results in differentiation of mESCs into parietal/visceral endoderm (Mitsui et al., 2003).

Type
Chapter
Information
MicroRNAs
From Basic Science to Disease Biology
 , pp. 476 - 488
Publisher: Cambridge University Press
Print publication year: 2007

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