Contents





Chapter 7 **Hepatocyte Selection Medium 165** Minoru Tomizawa, Fuminobu Shinozaki, Yasufumi Motoyoshi, Takao Sugiyama, Shigenori Yamamoto and Makoto Sueishi

Preface

Great progress continues to be made in our understanding of stem cell self-renewal and plu‐ ripotency, and the utilization of stem cells for basic and applied applications. This book em‐ bodies recent advances in the biological mechanisms, methods and models of stem cell selfrenewal, reprograming and regeneration, as well as touching on the ethical and moral dilemmas of embryo donation and adoption. In the first section of this book, 'Stem Cell Self-Renewal and Pluripotency', Agarwal and Zambidis examine the role of the NFκB-STAT3 signaling axis in regulating the induction and maintenance of the pluripotent state. The au‐ thors discuss a novel link between inflammatory pathways and efficient cell reprogram‐ ming, whereby bone marrow stromal-primed human myeloid cell progenitors are significantly more receptive to reprogramming stimuli than other cell types. Myeloid cells appear to harbor a unique epigenetic plasticity and are innately equipped to transcriptional‐ ly and epigenetically activate key inflammatory pathways via an interconnected NFκB and STAT3 signaling machinery. Both pathways act as epigenetic modifiers which promote ESC pluripotency by inducing an open chromatin state that allows transcription factors to regu‐ late cell fates. The importance of the NuRD complex in ensuring that differentiated cells do not reactivate pluripotency genes, which might enable tumorigenesis – is also discussed in this first chapter. The following chapter by Koide examines further the idea that many genes involved in ESC self-renewal also are involved in cancer cell growth. Considerable evidence supports the author's contentions, where self-renewal genes such as Oct 3/4, Sox2, Nanog, STAT3, Klf4 and Zfp57 are not only required for self-renewal in ESCs, but also are highly expressed in neoplastic cells. Conversely, there is evidence that oncogenes also are ex‐ pressed in SCs. That several common transcription factors are involved in the regulation of ESC self-renewal and cancer cell growth raises the intriguing possibility that these common transcription factors are specifically expressed in cancer stem cells involved in tumor growth. Moreover, the authors suggest that since ESCs and induced pluripotent stem cells (iPSCs) have similar gene expression profiles, tumor risk also might be elevated for iPSCs used for therapeutic purposes. As suggested by Agarwal and Zambidis, preventing cancer‐ ous epigenetic patterns in iPSC via more accurate high-fidelity reprogramming methods

In the next section on 'Haematopoiesis', Stefanska and colleagues review how ESCs have been used to study the development of the haematopoietic system, that is otherwise very difficult to study in vivo. As the authors write, 'ESCs have been instrumental in identifying and characterizing the elusive haemangioblast …. and more recently, this model system has allowed the merging of two conflicting theories of the origin of blood cells (haemangioblast and haemogenic endothelium) into a single linear model of development'. In addition, the precise roles and requirements of many critical regulators of this process have been elucidat‐

will be the foundation for future clinical applications.

