Cell Cycle Regulation and Differentiation in Cardiovascular and Neural Systems (eBook)

Preface 5
Contents 6
Contributors 8
Part I Introduction to Cell Cycle and Differentiation 11
1 Short Introduction to the Cell Cycle 12
1 Introduction 12
2 The G1 Phase 13
3 The S and G2 Phases 15
4 The M Phase 16
5 Cell Cycle Checkpoints 17
6 The G1 Checkpoint 17
7 The S Checkpoint 19
8 The G2 Checkpoint 19
9 The Spindle Checkpoint 19
References 20
2 The Basic Helix-Loop-Helix Transcription Factors in Neural Differentiation 24
1 Introduction 25
2 Maintenance of Neural Stem Cells by the Repressor-Type bHLH Genes: Hes 26
2.1 Structure and Transcriptional Activities of Hes Factors 26
2.2 Regulation of Hes Genes by Notch Signaling 28
2.3 Maintenance of Neural Stem Cells by Hes Genes 29
3 Neurogenesis by the Activator-Type bHLH Genes: Mash1, Math, Ngn, and NeuroD 33
3.1 Neuronal Determination and Subtype Specification 33
3.2 Combinatorial Functions of bHLH Genes for the Cell-Type Diversity 35
4 Gliogenesis by the bHLH Genes: Hes, Olig, and Scl 36
5 Cell Cycle Regulation and Boundary Formation by Hes1 37
6 Perspective 39
References 39
3 Transcription Factors and Muscle Differentiation 44
1 Introduction 45
2 Cellular Oncogenes 47
2.1 c-Jun and the AP-1 Complex 47
2.1.1 The c-Jun Myogenic Influence 49
2.2 The c-Myc Cellular Oncoprotein 50
2.2.1 c-Myc Is a Potent Inhibitor of Myoblast Differentiation 52
3 Ligand-Dependent Transcription Factors: Triiodothyronine Receptors 54
3.1 Triiodothyronine (T3) Nuclear Receptors 54
3.1.1 The TR Myogenic Influence 56
3.2 T3 Mitochondrial Receptors 57
3.2.1 P43: A Mitochondrial T3 Receptor Acting as a Ligand-Dependent Transcription Factor 58
3.2.2 The p43 Pathway Induces Irreversible Cell Cycle Arrest and Myoblast Differentiation 58
4 Targeting of Cellular Oncogenes by Ligand-Dependent Transcription Factors Regulates Myoblast Withdrawal from the Cell Cycle 59
4.1 TR Represses MyoD Transcriptional Activity in Proliferating Myoblasts 59
4.2 TR Only Represses AP-1 Activity at the Induction of Myoblast Differentiation 60
4.3 The Dual Myogenic Influence of TR Is Governed by RXR Expression 61
4.4 RXR Expression Also Reverses the Myogenic Influence of c-Jun Through TR-Dependent Mechanisms 61
4.4.1 BTG1, A Downstream Target of AP-1 Activity 62
4.5 c-Myc, a Target Involved in the Control of Myoblast Differentiation by Mitochondrial TR Isoforms 63
4.5.1 Regulation of Myoblast Differentiation Through the Mitochondrial Nuclear Crosstalk 65
5 Conclusions 66
References 67
Part II Stem Cells 78
4 The Neural Stem Cells 79
1 Endogenous Neural Stem Cells and CNS Diseases 81
2 Neural Stem Cell Transplantation and CNS Diseases 83
References 85
5 Cardiac Stem and Progenitor Cells 87
1 Introduction 88
2 Identification of Cardiac Stem/Progenitor Cells 89
2.1 Cardiac SP Cells 90
2.2 c-kit Positive Cardiac Cells 94
2.3 Sca1 + Cardiac Progenitor Cells 96
2.4 Islet 1 (Isl1) Positive Cardiac Cells 97
2.5 Cardiospheres 98
3 Origin of Cardiac Stem Cells 99
4 Cardiac Stem Cell Niche 100
5 Aging and Cardiac Progenitor Cells 103
6 The Role of Resident Cardiac Stem Cell in Repair and Regeneration 105
7 Conclusion and Future Prospective 105
References 106
6 Muscle Stem Cells 112
1 Introduction 112
1.1 Skeletal Muscle Regeneration as a Model to Study Stem Cell Function 112
1.2 Transcriptional Control of Muscle Development and Regeneration 113
1.3 Various Types of Stem Cells Contributing to Muscle Regeneration 114
2 Muscle Satellite Cells 114
2.1 Identification and Molecular Markers 114
2.2 Role of Pax7 in Satellite Cell Function 116
2.3 Regulation of Activation, Proliferation, Self-Renewal, and Differentiation 117
2.4 Multipotency of Satellite Cells 118
2.5 Satellite Cells as a Candidate for Stem Cell-Based Therapies 118
3 Other Myogenic Stem Cells Resident to the Muscle 119
3.1 Side Population Cells 119
3.2 Vessel-Associated Myogenic Progenitors 120
3.3 Interstitial Myogenic Progenitors 121
3.4 Myogenic Progenitors Non-resident to Muscle 122
3.5 A Possible Developmental Link Among Various Myogenic Stem Cells 122
4 Conclusions and Perspectives 123
References 124
7 Marrow Stromal Mesenchymal Stem Cells 128
1 Introduction 128
1.1 Adult Stem Cells 129
1.2 Bone Marrow-Derived MSCs 129
2 MSC Immunophenotype 130
3 Cell Cycle and Proliferation of MSCs 130
4 Mechanisms for Therapeutic Utility 132
4.1 Differentiation/Fusion 132
4.2 Paracrine-Mediated Effects 132
4.3 Modulation of Immune Responses 134
4.4 Anti-inflammatory Effects 134
5 Therapeutic Efficacy in the Heart and CNS 135
5.1 Central Nervous System 135
5.2 Cardiac Injury and Disease 137
References 138
Part III Cell Cycle and Differentiation in the Nervous System 146
8 Neurogenesis in the Central Nervous System: Cell Cycle Progression/Exit and Differentiation of Neuronal Progenitors 147
1 Pathways and Mechanisms of Differentiation in the Forebrain 148
1.1 The Role of Neural Stem Cells and Radial Glia During Embryonic Cortical Development 148
1.1.1 Neuroepithelial Cells 149
1.1.2 Radial Glial Cells 151
1.2 Symmetric Versus Asymmetric Cell Divisions During Neurogenesis 152
1.3 Brain Size Control 153
1.4 Cell Cycle Exit Signalling in the CNS 154
1.5 Proliferation and Cell Death During CNS Development 156
2 Pathways and Mechanisms of Differentiation in the Spinal Cord 157
2.1 Dorso-ventral Patterning in the Spinal Cord 158
2.1.1 Down-Regulation of FGF Signalling Induces the Onset of Neuronal Differentiation and Establishment of the Patterning System in the Spinal Cord 159
2.1.2 Ventral Patterning and Shh 159
2.1.3 RA Participates in Defining the Patterning in the Spinal Cord 163
2.1.4 Dorsal Patterning and BMPs 164
2.2 Specification of Neuronal Subtype Identities 165
2.2.1 Common Spinal Cord Patterning Mechanisms Operate to Specify Neurons and Glial Cells 166
3 Adult Neurogenesis 167
3.1 Adult NSC: Possible Candidates for CNS Repair? 169
3.2 Conclusions and Future Perspectives 170
References 170
Part IV Cell Cycle and Differentiation in the Cardiovascular System 182
9 Cell Cycle and Differentiation in the Cardiovascular System 183
1 Introduction 183
2 Normal Cardiac Cell Cycle Progression 185
2.1 Cardiac Myocyte Proliferation During Development 185
2.2 Expression of Cell Cycle Regulators During Cardiac Development 185
2.3 Transcriptional Control of Cardiac Cell Cycle E2F Family of Transcription Factors 188
2.4 The Myc-Mad Signaling Network 189
2.5 Forkhead Box O (FoxO) Transcription Factors 190
2.6 p300 191
3 Pathological Cardiac Cell Cycle Progression 192
3.1 Cardiac Cell Cycle Reactivation in the Adult Heart 192
3.2 Molecular Basis for Terminal Differentiation 193
4 Practical Implications and Therapeutic Perspectives 195
4.1 Potential for Cardiac Regeneration 195
4.2 Strategies to Reactivate the Cell Cycle in Adult Cardiac Myocytes 196
4.3 Recruitment and Expansion of Endogenous Cardiac Stem Cells 197
5 Summary and Conclusions 199
References 199
10 Cell Cycle and Differentiation in Vessels 207
1 Blood Vessel Development 207
2 Endothelial Cells: Cell Cycle and Differentiation 209
3 Smooth Muscle Cells: Cell Cycle and Differentiation 211
4 The Myofibroblasts: Origins and Functions 215
4.1 Myofibroblast Differentiation Pathways 217
4.2 What Stimulates Myofibroblast Differentiation? 219
4.3 Myofibroblast Ultimate Fate 219
5 The Role of Stem Cells in Vascular Pathophysiology 220
5.1 Mesenchymal Stem Cells 221
5.2 Endothelial Progenitor Cells 222
5.3 Smooth Muscle Progenitor Cells 222
5.4 Mesoangioblasts 223
5.5 Hemangioblasts 224
5.6 Bone Marrow Monocyte Lineage Cells 224
References 224
Part V Cell Cycle and Differentiation in the Muscle 233
11 Cell Cycle Regulation in Myogenesis 234
1 Introduction 234
2 Cell Cycle Overview 235
2.1 Cell Cycle 235
3 Cell Cycle and Myogenesis 237
3.1 Regulation of MyoD Function in Dividing Myoblast 237
3.2 Regulation of MyoD During Terminal Growth Arrest and Differentiation of Myoblasts 238
3.2.1 MyoD and Rb Functional Interaction 238
3.2.2 MyoD and Chromatin Remodeling Factors 239
3.3 Myogenesis and the CKIs 240
3.4 Differentiated Muscle Cells 241
3.5 Differentiation Checkpoint 241
4 Cell Cycle Deregulation in Muscle Cells 242
References 244
Subject Index 248