**Author details**

Hiroshi Koide\*

mechanism is that Akt induces expression of Tbx3, which in turn stimulates expression of

c-Myc is a cellular counterpart of the *v-myc* gene, which was isolated from the avian retrovirus MC29 [108], and belongs to a family of helix-loop-helix/leucine zipper transcription factors. c-Myc forms a complex with Max, which results in the increased stability of c-Myc protein [109]. Phosphorylation of Thr-62 by Erk also stabilizes c-Myc, while phosphorylation of Thr-58 by GSK3β reduces the stability of c-Myc [110]. c-Myc regulates expression of its target genes through binding to E-box sequences and recruiting histone acetyltransferases. Under normal conditions, when cells are stimulated by an internal or external growth-promoting signal, the level of c-Myc rapidly and transiently increases to induce cell proliferation, and the level of c-

It is well-established that many, if not most, human tumors have elevated levels of c-Myc owing to gene amplification and translocation [111, 112]. Gene amplification of *c-Myc* has been reported in several cancers, including breast, ovarian, and colon. A common human translo‐ cation involving *c-Myc* is t(8;14), which is critical for the development of Burkitt's lymphoma. Although c-Myc was one of the four factors originally identified as being required for iPS cell production [19], generation of iPS cells without this transcription factor has been reported

During the self-renewal of ES cells, levels of c-Myc are elevated [114]. By contrast, upon LIF withdrawal, the level of *c-Myc* mRNA decreases and c-Myc protein is phosphorylated on Thr-58 by GSK3β, which triggers degradation of c-Myc. Expression of a stable c-Myc mutant, in which the Thr-58 residue is mutated to alanine, allows ES cells to self-renew in the absence of LIF. By contrast, expression of a dominant-negative form of c-Myc inhibits the self-renewal of ES cells and induces their differentiation. These findings suggest that c-Myc is critically involved in maintaining the self-renewal of ES cells. Moreover, analysis of *Max*-null ES cells revealed that the function of c-Myc/Max in ES cell self-renewal seems to be largely independent

As I have described here, several common transcription factors are involved in the regulation of ES cell self-renewal and cancer cell growth (Fig. 2). This raises several intriguing possibilities. Considering that these common transcription factors are stem cell-specific and are involved in tumor growth, it is possible that they are specifically expressed in cancer stem cells and play important roles in the growth of these cells. Therefore, it is possible that these factors are good markers of cancer stem cells. If so, it might be possible to utilize these factors to isolate cancer stem cells, which will help to advance cancer stem cell research. Furthermore, identification of small compounds that specifically inhibit the functions of these factors may lead to the

development of new anti-cancer drugs that can selectively kill cancer stem cells.

Nanog to maintain ES cell self-renewal [107].

50 Pluripotent Stem Cell Biology - Advances in Mechanisms, Methods and Models

Myc subsequently returns to a low level in quiescent cells.

[113], suggesting that c-Myc is dispensable for cell reprogramming.

of the Oct3/4, Sox2, and Nanog regulatory networks [115].

**4. Future prospective**

**3.4. c-Myc**

Address all correspondence to: hkoide@med.kanazawa-u.ac.jp

Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan

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**Section 2**

**Stem Cells as a Model System for Studing**

**Haematopoiesis**

**Stem Cells as a Model System for Studing Haematopoiesis**

**Chapter 3**

**Embryonic Stem Cell**

Georges Lacaud

**1. Introduction**

http://dx.doi.org/10.5772/57607

**Differentiation – A Model System**

Monika Stefanska, Valerie Kouskoff and

Additional information is available at the end of the chapter

Haematopoiesis, the process of generation of blood cells, is one of the most extensively studied developmental systems. The whole spectrum of blood cells produced in mammalian organ‐ isms includes primitive erythrocytes and definitive haematopoietic cells such as myeloid,

Haematopoiesis takes place in several locations during ontogeny and in adult life. The embryonic origin of blood cells has been studied for more than a century. However, studies on haematopoiesis *in vivo* are challenging as embryos, and in particular mammalian embryos, are extremely small and difficult to access at these very early stages of development. Moreover, the number of cells per embryo is limited and all the successive developmental events take place very fast. Therefore different approaches have been developed to facilitate these studies *in vitro* and one of them involves the use of embryonic stem (ES) cell *in vitro* differentiation. In this chapter, we will highlight some recent results on studies of the development of the haematopoietic system obtained in particular using the *in vitro* differentiation of murine ES cells. We will also present the methods we routinely use in our laboratory to work with wild

> © 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

lymphoid, definitive erythroid and haematopoietic stem cells (HSCs).

type or genetically modified murine ES cells.

**to Study Embryonic Haematopoiesis**
