Regulation of Apoptosis and Differentiation by p53 in Human ...

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CHAPTER 1: Introduction TABLE 1.2- Published differentiation of hESC (Adapted from Hoffman and Carpenter, 2005) Cell Cell type Cell Note Reference lineage line General differentiation Endoderm, ectoderm and mesoderm derivatives H9.1 Formation of EBs followed by treatment with growth factor and analysis of expression of mRNA (Schuldiner et al., 2000) H9 H13 Expression of several markers by PCR and immunostaining Gene expression profile by microarray during differentiation (Itskovitz- Eldor et al., 2000) (Dvash et al., 2004) Ectoderm Neurons H9 RA and NGF neuronal differentiation (Schuldiner et al., 2001) Neurons and glia H1,H7,H 9 Differentiation into enriched populations of functional neurons and neural progenitors (Carpenter et al., 2001) Neurons and glia H1,H9, H9.2 Differentiation into neural progenitors, neurons and glia. Transplantation into (Zhang et al., 2001) neonatal rats Neurons and glia HES-1 Differentiation into neural progenitors, neurons and glia. Transplantation into neonatal rats Neurons BG01, BG02 Differentiation into neural precursors and neurons Neurons HES-1 Differentiation into dopaminergic neurons Transplantation into Parkinsonian rats, resulting in functional improvement Neural precursors HES-2, HES-3 Neurons H1, H9, HES-3 Differentiation into neural precursors Differentiation into midbrain dopaminergic neurons Differentiation into dopaminergic neurons (Reubinoff et al., 2001) (Schulz et al., 2003) (Ben-Hur et al., 2004) (Pera et al., 2004) (Perrier et al., 2004) Neurons BG01, BG03 (Schulz et al., 2004) Neurons BG01 Differentiation into dopaminergic neurons (Zeng et al., 2004) Neurons MB03 Differentiation into dopaminergic neurons (Park et al., 2004) Neurons H1,H9 Differentiation into motoneurons neurons (Li et al., 2005) Oligodendrocytes H7 Differentiation into enriched populations of oligodendrocytes and myelination after transplantation Endoderm Insulin positive cells Insulin-producing cells Hepatocyte-like cells Hepatocyte-like (Nistor et al., 2005) H9 Direct differentiation (Assady et al., 2001) H9, H9.2, H13, I6 Direct differentiation (Segev et al., 2004) H1, H9 Direct differentiation (Rambhatla et al., 2003) N/A Direct differentiation (Lavon et al., 2004) cells Mesoderm Cardiomyocytes H9.2 Evaluation of structural and functional properties (Kehat et al., 2001) Cardiomyocytes H9.2 High resolution electrophysiology (Kehat et al., 2002) Cardiomyocytes H1,H7,H9 Differentiation into enriched populations of functional cardiomyocytes (Xu et al., 2002a) Cardiomyocytes HES-2 Differentiation into cardiomyocytes and their characterization Cardiomyocytes H1,H7,H9, H14 14 Evaluation of electrophysiological and pharmacological properties Cardiomyocytes HES-2 Differentiation into cardiomyocytes by coculture with END-2 cells (Mummery et al., 2002), (Kehat et al., 2003) (He et al., 2003) (Mummery et al., 2003) - 16 -
CHAPTER 1: Introduction Cardiomyocytes H9.2 Evaluation of ultrastructural and proliferative characteristics Cardiomyocytes H9.2 Evaluation of electrophysiological and pharmacological properties Cardiomyocytes H1 Demonstration of functional integration after transplantation into guinea pig model Hematopoietic H1, H1.1, Differentiation of multipotent hematopoietic colony-forming H9.2 precursors cells Hematopoietic H1, H9 Differentiation of multipotent CD45 + progenitor cells hematopoietic precursors Hematopoietic H1, H9 Differentiation of multipotent CD34 + progenitor cells Hemangioblasts H1, H7, H9, MA01, MA03, MA40 and MA09) hematopoietic precursors Differentiation into multiple hematopoietic lineages and endothelial cells. Transplantation into rats and mice injured models, resulting in vascular repair Leucocytes H1 Differentiation into antige-presenting leucocytes Endothelial cells H9 Isolation and characterization of hESCderived endothelial cells Endothelial H1, H9 Identification of primitive endothelial-like cells that generate endothelial and hematopoietic cells Endothelial H9.2 Evaluation of endothelial markers during spontaneous differentiation Vasculogenesis H9.2, Vasculogenesis using alginate scaffolding H13 Vasculogenesis H9.2, Vasculogenesis in teratomas H13, I6 Extraembryonic Trophoblast H1, H7, H9, H14 Differentiation into trophoblasts (Snir et al., 2003) (Satin et al., 2004) (Xue et al., 2005) (Kaufman et al., 2001) (Chadwick et al., 2003) (Vodyanik et al., 2005) (Lu et al., 2007) (Zhan et al., 2004) (Levenberg et al., 2002) (Wang et al., 2004) (Gerecht-Nir et al., 2005) (Gerecht-Nir et al., 2004b) (Gerecht-Nir et al., 2004a) (Xu et al., 2002c) Trophoblast H1 Identification of trophoblast cells in EB (Gerami-Naini et al., 2004) Germ cells Germ cells HSF-1, HSF-6, H9 Spontaneous differentiation of stem cells (Clark et al., 2004) As seen from studies above, hESC have been vigorously investigated as a source for cell replacement therapies, and it is apparent that they can differentiate into a wide range of specific cell types. In order to deliver on their promise, large amounts of high quality hESC will be needed that are genetically stable, free of animal products and manipulated to evade the immune system through either somatic cell nuclear transfer or other technologies. A deeper understanding of the molecular mechanisms that control the genetic stability of hESC is required. - 17 -
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CHAPTER 3: Characterization of hESC
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CHAPTER 5: Conclusions and Future -
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CHAPTER 6: Bibliography - 128 -
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CHAPTER 6: Bibliography Benard, J.,
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CHAPTER 6: Bibliography Duensing, A
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CHAPTER 6: Bibliography Itskovitz-E
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CHAPTER 6: Bibliography Melino, G.,
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CHAPTER 6: Bibliography Rubinson, D
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CHAPTER 6: Bibliography Wei, C. L.,
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APPENDIX I - 144 -
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APPENDIX I 4% Paraformaldehyde (PFA
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TABLE A 2.1- List of genes upregula
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PMP22 1.76 0.70 NM_153322 PDE6G 1.8
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TABLE A 2.2- List of functions of u
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Protein Synthesis Ophthalmic Diseas
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1.73 0.897 CN292254 LOC651029 1.73
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Reproductive System Disease Cellula
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