Stem Cell Biology and Regenerative Medicine Charles Durand, Pierre Charbord, second edition

The study of stem cell biology is under intensive investigation. Because stem cells have the unique capability to self-renew and differentiate into one or several cell types, they play a critical role in development, tissue homeostasis and regeneration. Stem cells also constitute promising cell candidates for cell and gene therapy.The aim of this book is to provide readers and researchers with timely and accurate knowledge on stem cell biology and regenerative medicine. This book will cover many topics in the field and is based on conferences given by recognized scientists involved in the international master course on stem cell biology at Sorbonne Université in Paris. Front Cover Stem Cell Biology and Regenerative Medicine Contents Preface List of Figures List of Tables List of Contributors List of Abbreviations 1 Stem Cell Concepts 1.1 Introduction 1.2 Embryonic and Adult Stem Cells 1.3 The Regulation of Stem Cells and the Stem Cell Niche 1.4 Stem Cell Models 1.5 Cell Therapy Using Stem Cells 1.6 Concluding Remarks Acknowledgments References 2 Transcription Regulation by Distal Enhancers: Dynamics of the 3D Genome 2.1 Introduction 2.2 Spatio-temporal Control of Gene Activity: The Pivotal Role of Enhancers 2.3 The Genome-wide Enhancer Landscape 2.4 Enhancer Dynamics 2.5 Enhancers and Promoters Are Distant Structures 2.6 Mechanisms of Enhancer Function: The 3D Genome 2.7 Dynamic versus Stable Chromatin Looping 2.8 Transcription Factories or Foci 2.9 Specificity of Enhancer–Promoter Contacts 2.10 TADs: Topologically Associating Domains 2.11 Functional Relevance of TADs and Their Borders 2.12 Alterations of Enhancers and 3D Genome Organization in Disease 2.13 Concluding Remarks Acknowledgements References 3 Repair of DNA Double-Strand Breaks in Adult Stem Cells 3.1 Introduction 3.2 DNA Damage and Repair Mechanisms 3.3 Cell Response to DSBs 3.4 Stem Cells Resistance to Genotoxic stress 3.5 Efficiency and Mechanisms of DSB Repair in Adult Stem Cells 3.6 Other Responses to DNA Damage 3.7 Concluding Remarks References 4 Haematopoietic Stem Cell Niches in the Bone Marrow 4.1 Haematopoietic Stem Cell Niches 4.2 The Contribution of Structural Components 4.3 Concluding Remarks Acknowledgments References 5 Computational Models of Spatio-temporal Stem Cell 5.1 Introduction 5.2 Concepts of Stem Cell Organization 5.3 Intestinal Stem Cell Organization as a Paradigm 5.4 Models of Epigenetic Regulation 5.5 Stem Cells During Development and Aging 5.6 Stem Cells in Artificial Environments 5.7 Summary 5.8 Concluding Remarks Acknowledgement References 6 Transcriptomics Investigations 6.1 From Omics to Data 6.2 Data Analysis and Standardization in Omics 6.3 Study of Transcriptomes Using Microarrays 6.4 Study of Transcriptomes Using Next Generation Sequencing (NGS) 6.5 Study of Single Cell Transcriptomes 6.6 Network Biology 6.7 Machine Learning Classifiers 6.8 Conclusion References 7 The Regulatory Network of X Chromosome Inactivation 7.1 Introduction 7.2 The X:Autosome Ratio Dictates Initiation of XCI 7.3 Initiating X-Inactivation, the Regulatory Environment of the XIC 7.4 The Pluripotency Network and Other Trans-acting Factors of XCI 7.5 The Balancing Act of Activators and Inhibitors in Initiation of XCI 7.6 Concluding Remarks References 8 Directed Differentiation of Human-induced Pluripotent Stem Cells into Hepatic Cells: A Transposable Example of Disease Modeling and Regenerative Medicine Applications 8.1 Introduction 8.2 Developmental Origins of the Liver 8.3 hiPSCs and Directed Differentiation In Vitro 8.4 hiPSC-derived Liver Cell Applications 8.5 Concluding Remarks References 9 Hydra and the Evolution of Stem Cells 9.1 Introduction 9.2 The “Mystery” of Hydra’s Life Cycle 9.3 Revisiting Stem Cells in Hydra with Emerging 9.4 Stem Cells in Hydra Are Controlled by Conserved 9.5 Epigenetic Control of the Stem Cells in Hydra 9.6 Taxonomically Restricted Genes (TRGs) Have Their 9.7 Stem Cells Interact with the Environment 9.8 Microbiome Contributes to Tumor Formation 9.9 Open Questions and Future Perspectives 9.10 Concluding Remarks References 10 Regeneration in Anamniotic Vertebrates 10.1 Introduction 10.2 Appendage Regeneration in Amphibians 10.3 Other Examples of Regeneration 10.4 Regeneration and Metabolism 10.5 Concluding Remarks Acknowledgments References 11 Stem Cells and Regeneration in Plants 11.1 Introduction 11.2 SAM Organization and Regulation 11.3 RAM Organization and Regulation 11.4 SAM Regeneration 11.5 Concluding Remarks 11.6 Take on Messages References 12 Hematopoietic Development in Vertebrates 12.1 History of the Concept of HSCs 12.2 On the Origin of Blood 12.3 An Intra-embryonic Source of HSCs 12.4 Construction of the Aorta and Establishment of the Dorsoventral Polarity 12.5 Role of the Sub-aortic Mesenchyme 12.6 IAHC Formation is a Conserved Mechanism in Vertebrates 12.7 BM ECs Can Generate a Transient Wave of HSPCs 12.8 Systems Used to Study Hematopoietic Cell Commitment 12.9 Concluding Remarks Bullet Points References 13 Developmental Biology of Hematopoietic Stem Cells: Non-cell Autonomous Mechanisms 13.1 Introduction 13.2 Developmental Niches 13.3 Cell-intrinsic Factors of Hematopoietic Stem Cell Generation 13.4 Supporting Nascent Hematopoietic Stem Cells 13.5 Future Directions 13.6 Conclusions References 14 Biology of Hematopoietic Stem Cells in the Adult 14.1 Definition, Concepts, History 14.2 Characterization of HSC 14.3 Regulation of HSC Functions 14.4 Ex Vivo Expansion of HSPC 14.5 Conclusive Remarks and Perspectives Acknowledgments References 15 Epithelial Stem Cells in the Skin 15.1 Introduction 15.2 The Interfollicular Epidermis 15.3 The Hair Follicle 15.4 Contribution of Bulge Stem Cells to the Epidermis 15.5 Contribution of Bulge Stem Cells to the Sebaceous Gland Lineage 15.6 The Sweat Gland 15.7 Concluding Remarks References 16 Mammary Stem Cells 16.1 Introduction 16.2 The Mammary Epithelium and Its Stem Cells 16.3 Lineage Tracing Analysis to Study Stem Cells In Vivo and In Situ 16.4 Mammary Cell Plasticity 16.5 Molecular Signals Governing MaSCs and Gland Morphogenesis 16.6 Concluding Remarks References 17 The Intestinal Stem Cells in Homeostasis and Repair 17.1 Introduction 17.2 Different Overlapping Populations of Stem Cells Ensure Homeostasis of the Adult Intestine 17.3 The Multiple Strategies to Protect and Repair the Intestinal Barrier 17.4 The Fine-tuning of Intestinal Stem Cells Fate 17.5 Bugs in the Niche 17.6 Perspectives on ISCs-based Regenerative Medicine 17.7 Concluding Remarks References 18 Neural Stem Cells 18.1 Introduction 18.2 Evidencing Postnatal Neurogenesis in Mammals 18.3 Neural Stem Cells Lie in Specific CNS Regions 18.4 Ecology of Neural Stem Cells 18.5 Concluding Remarks References 19 Non-hematopoietic Stem Cells of Bone and Bone Marrow 19.1 Historical Background 19.2 Bona fide Murine Stem Cells 19.3 Stem Cells in Human Adult Bone and BM 19.4 A Stem Cell for Mesenchymal Stem Cells? 19.5 Models of Stem Cell Differentiation: Hierarchical or Plastic? 19.6 Concluding Remarks Acknowledgments References 20 Dental Stem Cells 20.1 Introduction 20.2 State of the Art 20.3 Major Unsolved Problems and Ongoing Controversies in the Field 20.4 True Nature of DPSCs 20.5 Fate of Implanted Dental Stem Cells in Tissue Repair 20.6 Contribution of the Team to the Field: DP Stem Cells and Craniofacial Bone Repair 20.7 Perspectives 20.8 Concluding Remarks Acknowledgments References 21 Stem Cells and Retina: From Regeneration 21.1 Introduction 21.2 Eye Morphogenesis and Retinogenesis 21.3 Adult Retinal Stem Cells and Neurogenic Potential 21.4 The CMZ: a Retinal Stem Cell Niche 21.5 The Neurogenic Potential of the RPE 21.6 The Müller Glial Cells: A Retinal Stem 21.7 Cell Replacement for Retinal Repair 21.8 Concluding Remarks References 22 Glioblastoma Stem Cells 22.1 Introduction 22.2 GBM initiation 22.3 Identification of GSCs 22.4 Regulation of GSC Activity 22.5 GSC Heterogeneity and Plasticity 22.6 GSC Resistance to Therapies 22.7 Concluding Remarks Acknowledgments References 23 Cardiac Tissue Engineering for Repair and Regeneration of the Heart 23.1 Introduction 23.2 Heart Diseases and Stem Cell-based Therapies 23.3 The Heart: A Complex Organ 23.4 Cell Types for Heart Repair: An Endless Story? 23.5 The Rise of Pluripotent Stem Cells-derived 23.6 Cardiomyocytes Subtypes of hPSC-derived Cardiomyocytes 23.7 Maturation of hPSC-derived Cardiomyocytes 23.8 Biomaterials for Stem Cell 23.9 New Perspectives in Cardiac Tissue 23.10 Concluding Remarks Key Points References 24 Stem Cells for Red Blood Cell Production 24.1 Introduction 24.2 Erythropoiesis 24.3 From RBCs to Transfusion and Back to Blood Substitutes 24.4 The Cell Engineering Era 24.5 The Gene Editing Era 24.6 Conclusion Concluding Remarks References 25 Prospectives for TherapyWith Stem Cells in Skeletal Muscular Diseases 25.1 Introduction 25.2 What Is Expected From a Good Cell Candidate? 25.3 Candidate Cells 25.4 Therapeutic Application and Future Optimization 25.5 Concluding Remarks References 26 Legal Framework for Research on Human Embryonic Stem Cells in France and in Europe 26.1 Introduction 26.2 How to Regulate hESC Research? The French Example 26.3 Examples of Regulations in Europe: France’s Neighbors 26.4 Concluding Remarks References 27 Stem Cell Conceptual Clarifications 27.1 Introduction 27.2 Stem Cell Definition 27.3 Self-Renewal and Differentiation Definition 27.4 Proving Stemness: The Uncertainty Principle 27.5 Natural Kind or Artificial Grouping 27.6 Does the Concept of Stem Cell Refer to an “Entity” or to a Cell “State”? 27.7 Stemness Ontology: Not Two but Four 27.8 Philosophy Matters 27.9 Concluding Remarks Highlights Acknowledgments References 28 Future Outlook 28.1 Introduction 28.2 Understanding and Capturing Pluripotency 28.3 Integrating Signals of Intrinsic, Extrinsic and Systemic Origins 28.4 Stem Cell Heterogeneity and Plasticity 28.5 Interface Between Stem Cell and Computational Biology 28.6 Therapeutic Applications of Stem Cells References Index About the Editors Back Cover Copyright Title Page Dedication Contents Chapter 1: ‘I’m thinking’ – Oh, but are you? Chapter 2: Renegade perception Chapter 3: The Pushbacker sting Chapter 4: ‘Covid’: The calculated catastrophe Chapter 5: There is no ‘virus’ Chapter 6: Sequence of deceit Chapter 7: War on your mind Chapter 8: ‘Reframing’ insanity Chapter 9: We must have it? So what is it? Chapter 10: Human 2.0 Chapter 11: Who controls the Cult? Chapter 12: Escaping Wetiko Postscript Appendix: Cowan-Kaufman-Morell Statement on Virus Isolation Bibliography Index The study of stem cell biology is under intensive investigation. Because stem cells have the unique capability to self-renew and differentiate into one or several cell types, they play a critical role in development, tissue homeostasis and regeneration. Stem cells also constitute promising cell candidates for cell and gene therapy. The aim of this book is to provide readers and researchers with timely and accurate knowledge on stem cell biology and regenerative medicine. This book will cover many topics in the field and is based on conferences given by recognized scientists involved in the international master course on stem cell biology at Sorbonne Université in Paris