Male Germline Stem Cells: Developmental and Regenerative Potential (eBook)

Male Germline Stem Cells:Developmental andRegenerative Potential 3
Foreword 5
Contents 9
Contributors 15
Part I:Germline Developmental Potential 19
Chapter 1: Pathways to Pluripotency: How Germ Cells Make Stem Cells 20
1.1 Introduction 20
1.2 Early Germ Cell Development 22
1.3 How It All Goes Wrong 24
1.4 Probing the Mechanisms of Pluripotency 27
1.5 Lessons from Testicular Cancer 32
1.6 Parallel Pathways to Pluripotency 37
References 38
Chapter 2: Pluripotent Stem Cells from the Postnatal Testis: Unlocking the Potential of Spermatogonial Stem Cells 42
2.1 Introduction 42
2.2 The Putative Precursors: Spermatogonial Stem Cells (SSCs) 43
2.3 Molecular Features that Could Predispose SSCs to Pluripotency 44
2.4 Epigenetic Factors that Could Predispose to Pluripotency 47
2.5 Culture-Induced Pluripotency in Mice 48
2.6 Culture-Induced Pluripotency in Humans 53
2.7 Potential Applications of Germline-Derived Pluripotent Cells: A Comparison with ES Cells and iPS Cells 55
2.8 Conclusions 58
2.9 Addendum 59
References 59
Chapter 3: Making Germ Cells from Human Embryonic Stem Cells 65
3.1 Introduction 66
3.2 The Formation and Differentiation of Gametes In Vivo 68
3.2.1 Germ Plasm Versus Inductive Signaling 68
3.2.2 The Morphological Features of Gamete Development 69
3.2.3 The Molecular Requirements of Germ Cell Development 71
3.3 The DAZ Gene Family 73
3.3.1 The Y Chromosome DAZ Genes 73
3.3.2 DAZ Family Genes Are Evolutionarily Conserved and Function in Gametogenesis 74
3.4 The Generation of Germ Cells from ES Cells In Vitro 78
3.4.1 Similarities Between ES Cells and Germ Cells 79
3.4.2 Can Human ES Cells Give Rise to Germ Cells? 80
3.4.3 Generation of Mouse Germ Cells and Gametes In Vitro 82
3.4.4 Generation and Isolation of Human Germ Cells In Vitro 84
3.5 Genetic Requirements of Making Germ Cells 88
3.5.1 Key Germ Cell Genes 88
3.5.2 Definitive Proof of Mature Germ Cell Formation 91
3.6 The Future: Improved Methods and Clinical Implications 93
3.6.1 Improving Culture Conditions for Enhanced Gamete Formation 93
3.6.2 Clinical Implications and Outlook 93
References 95
Part II:Spermatogonial Stem Cells 103
Chapter 4: Morphometric Description of Spermatogonial Stem Cells and Expansion of Their Clonal Derivatives 104
4.1 Outline 105
4.2 Introduction 105
4.3 Scheme of Spermatogonial Multiplication and Stem Cell Renewal 106
4.4 Morphological Characteristics of As,.pr,.al Spermatogonia 107
4.5 Numbers of As,pr,al Spermatogonia During the Epithelial Cycle 110
4.6 Cell Cycle Characteristics of As,pr,al Spermatogonia 111
4.7 The Occurrence of “False” Pairs of Spermatogonia 113
4.8 Proliferative Activity of As, Apr, and Aal Spermatogonia During the Epithelial Cycle 114
4.9 Regulation of the Proliferative Activity of As, Apr, and Aal Spermatogonia at the Cellular Level 115
4.10 Regulation of Spermatogonial Numbers 117
4.11 Conclusion 118
References 118
Chapter 5: Spermatogonial Stem Cell Transplantation and Culture 121
5.1 Introduction 122
5.2 Spermatogonial Stem Cell Transplantation 122
5.2.1 History 122
5.2.2 Implications 122
5.2.3 Clonality and Quantification 124
5.2.4 Species Specificity 124
5.2.4.1 Rodent 124
5.2.4.2 Non-rodents 124
5.2.5 Procedures and Considerations 125
5.2.5.1 Cell Labeling and Enrichment 125
5.2.5.2 Homing Efficiency 126
5.2.5.3 Recipient Preparation and Injection 128
5.3 Spermatogonial Stem Cell Culture 129
5.3.1 History 129
5.3.2 Implications 130
5.3.3 Short- Versus Long-Term Culture 130
5.3.4 Species 133
5.3.4.1 Rodent 133
5.3.4.2 Non-rodent 134
5.4 Summary 134
References 134
Chapter 6: The Cluster-Forming Activity Assay: A Short-Term In Vitro Method to Analyze the Activity of Mouse Spermatogonial Stem Cells 138
6.1 Parallelism Between the Results of In Vitro and In Vivo SSC Assays 139
6.2 Advantages of the CFA Assay 141
6.3 Cautionary Issues 142
6.3.1 Does the CFA Assay Assess the Full Range of Stem Cell Characteristics? 142
6.3.2 Do Clusters Arise Only from SSCs? 142
6.3.3 Does the Number of Cells Placed in Culture Affect Assay Outcomes? 143
6.3.4 Can the CFA Assay Distinguish SSC Proliferation and Maintenance? 143
6.3.5 Is Cluster Number the Only Readout of the CFA Assay? 145
6.3.6 Other Considerations 145
6.4 Future Prospects 146
References 146
Chapter 7: Molecular Mechanisms Regulating Spermatogonial Stem Cell Fate Decisions 148
7.1 Spermatogenesis and Spermatogonial Stem Cell Biology 149
7.2 Extrinsic Growth Factor Regulation of SSC Self-renewal 152
7.2.1 GDNF 152
7.2.2 FGF2 and CSF1 154
7.3 Internal Molecular Pathways Regulating SSC Self-Renewal 154
7.3.1 GDNF-Regulated Gene Expression in Mouse SSCs 155
7.3.2 GDNF-Regulated Transcription Factors 156
7.3.2.1 BCL6B 156
7.3.2.2 ETV5 157
7.3.2.3 LHX1 157
7.3.2.4 OCT6 158
7.3.3 Non-GDNF Regulated Transcription/Translation Factors 158
7.3.3.1 MILI 158
7.3.3.2 NANOS2 159
7.3.3.3 OCT3/4 160
7.3.3.4 PLZF 160
7.3.3.5 TAF4B 162
7.3.4 Transcription Factors with Putative Roles in SSC Differentiation 162
7.3.4.1 NGN3 163
7.3.4.2 SOHLH1 163
7.4 GDNF-Activated Signaling Pathways in Cultured Mouse SSCs 163
7.5 Summary 164
References 166
Chapter 8: Stem Cell Niche System in Mouse Spermatogenesis 171
8.1 Introduction 171
8.2 Drosophila Germline Stem Cell Niche System 172
8.3 Architecture of the Mouse Testis 174
8.4 Mouse Spermatogenic Stem Cells 176
8.5 Niche Microenvironment in the Mouse Testis 178
8.6 Molecular Mechanisms That Could Be Involved in the Niche Functions 181
8.6.1 Soluble Factors 181
8.6.1.1 GDNF (Glial Cell Line-Derived Neurotrophic Factor) Signaling 181
8.6.1.2 CSF1 (Colony Stimulating Factor 1/Macrophage Colony-Stimulating Factor or M-CSF) Signaling 182
8.6.2 FGF (Fibroblast Growth Factor) and Other Factors 183
8.7 Cell–Cell Contact and Basement Membrane Binding 183
8.8 Transcriptional Regulator in Somatic Cells 184
8.8.1 Etv5 (ets Variant Gene 5/ERM or ets-Related Molecule) 184
8.9 Conclusion 184
References 185
Part III: Translation and Regenerative Potentialof Spermatogonial Stem Cells 188
Chapter 9: Regenerative Potential of Spermatogenesisafter Gonadotoxic Therapies 189
9.1 Introduction 189
9.2 Immediate and Short-Term Effects of Gonadotoxic Therapies 190
9.3 Stem Spermatogonial Survival–Methods 192
9.4 Stem Spermatogonial Survival-Results 193
9.4.1 Counts of Type A Spermatogonia 193
9.4.2 Assessing Stem Cell Survival by Recovery Potential 194
9.4.3 Functional Assay of Stem Cells by Transplantation 197
9.5 Recovery of Spermatogenesis from Surviving Stem Spermatogonia 197
9.6 Modulation of the Regenerative Process 201
9.7 Analysis of Interspecies Differences 204
9.8 Conclusion 206
References 207
Chapter 10: Testicular Xenografting 214
10.1 Introduction 215
10.2 Testicular Tissue Grafting: A Comparative Overview 216
10.3 Testicular Xenografting Using Testicular Cell Suspensions 227
10.4 Xenografting of Primate Testicular Tissue: Clinical and Experimental Perspectives 228
References 231
Chapter 11: Translating Spermatogonial Stem Cell Transplantation to the Clinic 235
11.1 Introduction—Clinical Possibilities for Male Fertility Preservation 236
11.2 Primate Spermatogonial Stem Cells 239
11.3 Nonhuman Primate Model for Developing SSC Transplantation 240
11.3.1 SSC Transplantation in Rodents 240
11.3.2 Primate Testis Cell Isolation 241
11.3.3 Cryopreservation 242
11.3.4 Recipient Models for SSC Transplantation 244
11.3.5 Busulfan Treatment 244
11.3.6 Testicular Irradiation 246
11.3.7 Ultrasound-Guided Rete Testis Injection 246
11.3.8 Definitive Autologous SSC Transplants in Primates 249
11.3.9 Allogeneic SSC Transplants 249
11.4 Clinical Implications and Considerations for SSC Transplantation 251
11.4.1 Patient Testis Accrual 251
11.4.2 Testis Cell Isolation in the Clinic 252
11.4.3 Human SSC Culture 252
11.4.4 Risk of Reintroducing Malignant Cells During SSCs Transplants 253
11.4.5 Ethical Considerations 254
11.5 Conclusions 256
References 256
Index 262