Chapter
5.3 Transcriptome-Wide Expression Analysis Points toFunctional Cross Talk between Cells of the ThreeStem Cell Lineages
5.4 Taxonomically Restricted Genes (TRGs) HaveTheir Saying
5.5 Stem Cells in Hydra are Controlled by Both Conservedand Non-Conserved Transcription Factors
5.6 Decision Making in Hydra Stem Cells: Rolesof Wnt and FoxO
5.7 Stem Cells and Immunity
5.8 Evolutionary Considerations
5.9 Future Prospects in Stem Cell Biology: How Do StemCells Respond to External Signals and MetabolicState?
Chapter 6 - Ontogeny of Stem Cells
6.1.1 Stem Cells; Problems and Definitions
6.1.2 Totipotent Stem Cells
6.1.3 Pluripotent Stem Cells
6.1.4 The Loss of Pluripotency and the First Commitment Events
6.1.5 Multipotent, Oligopotent and Unipotent Stem Cells
6.1.6 Ontogeny of Stems Cells: A Few Examples
6.1.7 Neural Crest Cells and Stem Cells
6.1.7.2 Clonal analysis of the NC population
6.1.7.3 Organ-resident NC-derived stem cells
6.1.8 Construction of the Aorta and Control of AorticHaematopoiesis
6.1.8.1 Hemogenic vs non-hemogenic endothelium
6.1.8.2 Somites and their role(s) in aortic maturation
6.1.8.3 The Sub-aortic mesenchyme triggers the onset of aortichaematopoiesis
Chapter 7 - Regeneration in Anamniotic Vertebrates
7.2 Limb Regeneration in Amphibians
7.2.1 Launching Regeneration viaWounding
7.2.2 Role of the Nerves in Inducing Blastema
7.2.3 Role of Positional Discontinuity in Blastema Maintenance
7.3 Cellular Sources and Differentiation Potentialof Blastema Cells
7.3.1 Dedifferentiation Versus Stem Cell Activation – SkeletalMuscle in Salamanders
7.3.2 Regeneration via Alternative Sources of Progenitors -Zebrafish Fin Bone
7.4 Specification and Re-specification of PositionalInformation
7.5 Frogs - Regenerative Capacity Dependson Developmental Stage
7.6 Other Examples of Regeneration
7.6.2 Lens Regeneration in Amphibians via Transdifferentiation
Chapter 8 - Computational Models of Spatio-temporalStem Cell Organization
8.2 Chapter 1: Concepts of Stem Cell Organization
8.3 Chapter 2: Extrinsic Stem Cell Regulation:The Intestinal Epithelium
8.4 Chapter 3: Intrinsic Stem Cell Regulation:Mesenchymal Stem Cells
8.5 Conclusions and Outlook
Part 2 - Pluripotent Stem Cells
Chapter 9 - X Chromosome Inactivation in Stem Cellsand Development
9.2 Dosage Compensation inWorms, Flies and Birds
9.3 Dosage Compensation by X Chromosome Inactivation
9.4 Stem Cells as a Model for XCI
9.5 The X Inactivation Center
9.6 Models for XCI Initiation
9.7 Trans-acting Factors in XCI
9.8 Chromosome-Wide Silencing of the X Chromosome
9.9 Induced Pluripotent Stem Cells as a Model for XChromosome Reactivation
9.9.1 X Chromosome Reactivation in Embryonic Development
9.10 In Vitro X Chromosome Reactivation: Somatic CellsReprogramming
Chapter 10 - The Molecular Machinery of Somatic CellReprogramming
10.2 Timeline of the Main Events During Reprogramming
10.2.1 The Stochastic Early Phase of Somatic CellReprogramming
10.2.1.1 Early epigenetic events involved in reprogramming
10.2.1.2 Early transcriptional changes
10.2.1.3 Metabolic switch
10.2.1.4 Transgene independence
10.2.2 The Deterministic Late Phase Of Somatic CellReprogramming
10.2.2.1 Intermediate events
10.2.2.2 Telomere elongation
10.2.2.3 A second wave of epigenetic modifications
10.2.2.5 X chromosome reactivation
10.3 Signaling Pathways Changes Associated withSomatic Cell Reprogramming
10.4.1 Reprogramming Systems for Improved Efficiency andQuality of iPSCs
10.4.2 Reprogramming Towards a Naive State Using OnlyChemical Compounds
10.4.3 Reprogramming by Stress
10.5 Conclusions and Challenges for Future ClinicalApplications of iPSCs
Chapter 11 - Modeling Human Genetic Disorders UsingInduced Pluripotent Stem Cells
11.1 Choice of the disease to model into a Petri Dish
11.2 Selection of the Cell Type to Reprogram
11.3 Derivation and Characterization of iPSCs
11.4 Differentiation into the Relevant Cell Type
11.5 Characterization of The Disease Phenotype
Part 3 - Adult Stem Cells
Chapter 12 - Developmental Biology of HematopoieticStem Cells: Cellular Aspects
12.2 The Hemangioblast Concept and the Yolk Sac Blood Islands
12.3 The Yolk Sac, Placenta and Embryo Proper Can De Novo Generate Hematopoietic Progenitors
12.4 HSCs are First Detected in the Aorta, Vitelline and Umbilical Arteries
12.5 The Hemogenic Endothelium is at the Origin of All HSCs
12.6 HSC Maturation, Expansion and Colonization
Chapter 13 - Developmental Biology of Haematopoietic Stem Cells: Cell Intrinsic and Extrinsic Regulators of Their Emergence
13.3 Cell Intrinsic Factors
13.4 The Micro environment
13.4.3 Mesenchymal Stem/Stromal Cells
13.4.4 Signals from the Developing Gut
13.4.5 Sympathetic Nervous System
13.4.6 Dlk1-Expressing Cells
13.4.7 Other Soluble Extrinsic Factors
Chapter 14 - Biology of Hematopoietic StemCells in the Adult
14.1 Definition, Concepts, History
14.2 Characterization of HSC
14.2. 1 II-A Phenotypic Analysis
14.2.2.1 Colony forming cells (CFC)
14.2.2.2 Long-term culture initiating cells (LTC-IC)
14.2.2.3 Liquid cultures and lymphoid progenitors
14.2.2.4 Multipotent progenitors in vitro
14.2.2.5 In vivo reconstituting cells
14.2.3.1 Self-renewal and quiescence properties
14.3 Regulations of HSC Functions
14.3.1 Extrinsic Regulators
14.3.1.2 SCF and its receptorc-Kit
14.3.1.3 Integrins and adhesion molecules
14.3.1.5 Wingless-type (Wnt) pathway
14.3.2 Intrinsic Regulators (See Also (Orkin and Zon, 2008))
14.4 Ex Vivo Expansion of HSPC
14.4.1 Extrinsic Factors for Ex Vivo HSPC Expansion
14.4.1.1 Usage of cytokines and growth factors’ combination
14.4.1.2 Expansion in presence of stromal cells
14.4.2 Developmental and Intrinsic Factors for Ex Vivo HSPC Expansion
14.4.2.1 Preclinical approaches
14.4.2.2 Clinical approaches
14.4.3 Chemical Compounds for Ex Vivo HSPC Expansion
Chapter 15 - Epithelial Stem Cell in the Skin
15.2 The Interfollicular Epidermis
15.2.1 Development of the IFE
15.4 Contribution of Bulge Tem Cells to the Epidermis
15.5 Contribution of Bulge Stem Cells to the SebaceousGland Lineage
15.6 The Sweat Gland (SwG)
Chapter 16 - Skeletal Muscle Stem Cells
16.1.1 Satellite Cells, the Functional Progenitor of Striated Muscle
16.3 Muscle Regeneration is a Complex Process Involving Cross talk between Different Cell Types
16.4 Muscle Regeneration with Age
16.5 Muscular Dystrophies
Chapter 17 - Mammary Stem Cells
17.1 Mammary Morphogenesis
17.2 Pioneering Experiments Suggesting the Existence of Mammary Stem Cells
17.3 Separation of Mammary Epithelial Cell Populations by Flow Cytometry
17.4 Experimental Techniques Used to Assess Mammary Stem and Progenitor Cell Activities
17.5 Basal Multipotent Stem Cells, Luminal Progenitors and Luminal Mature Cells
17.5.1 The Mammary Epithelial Cell Hierarchy, As Unraveled By In Vivo Lineage Tracing
17.5.2 Regulators of Mammary Stem and Progenitor Cell Function
17.5.2.1 Ovarian hormones
17.5.2.2 Integrin-mediated interactions with ECM
17.5.2.3 The Wnt signaling
17.5.2.4 The EMT program and stemness
17.5.3 The Transcription Factor P53
17.5.4 The Notch Pathway and Regulation of the Balance Between Basal and Luminal Lineages
17.5.5 Gata3, a Critical Regulator of the Luminal Lineage
17.5.6 Elf5, a Major Regulator of Alveologenesis
17.5.7 The Signal Transducer and Activator of Transcription (Stat) Family
17.5.8 Epigenetic Regulation
Chapter 18 - Intestinal Stem Cells
18.2 The Intestinal Epithelium and its Stem Cells
18.2.1 Intestinal Stem Cells (ISCs)
18.2.2 Different Types of ISCs and Major Outstanding Questions
18.2.3 ISCs and Regenerative Medicine
18.2.4 Notch Signalling and ISCs
Chapter 19 - Neural Stem Cells
19.1 Evidencing Postnatal Neurogenesis in Vertebrates
19.1.2 Markers of Neurogenesis
19.1.3 The Bomb and The Brain
19.1.4 In Vitro Culture for Neural Stem Cells
19.2 Neural Stem Cells Lie in Specific CNS Regions
19.2.1 Stem Cells in the Subventricular Zone
19.2.2 Stem Cells in the Subcallosal Zone
19.2.3 Stem Cells in the Dentate Gyrus of the Hippocampus
19.2.4 Neural Stem Cells in the Spinal Cord
19.3 Ecology of Neural Stem Cells
19.3.1 Neural Stem Cells Live in a Niche
19.3.2 Regulation of the Niche by Bone Morphogenetic Proteins (BMPs)
19.3.3 When Endothelial Cells Meet Neural Stem Cells
Chapter 20 - Dental Stem Cells
20.2.1 The Dental Pulp Contains MSC-like Cells Capable to Assume Various Fates In Vitro and to Participate in Tissue Repair In Vivo
20.3 Major Unsolved Problems and on Going Controversies in the Field
20.3.1 Heterogeneity in Pulpal Cell Populations
20.3.1.1 Truenature of DPSCs
20.3.1.2 Fate of Implanted Dental Stem Cells in Tissue Repair
20.3.1.3 Alternative Potential Stem Cells for the Tissue Engineering of the Tooth
20.4 WhichDental Stem Cells for Whole Tooth Tissue Engineering?
20.4.1 DPSCs and Dental Epithelium Reassociations
20.4.1.1 The Pluripotent Stem Cells: An Alternative Cell Population for Tooth Tissue Engineering
Chapter 21 - Bone Marrow Mesenchymal Stem Cells:from Stemness to Stromal Property ofHematopoietic Support
21.2.2 Quiescence and Proliferative Capacity
21.2.4 Differentiation Potential
21.2.5 Regenerative Capacity of Injured Tissues
21.2.6 Isolation and Population of Origin
21.3 BMMSCs as Stromal Cells
21.4 Our Contribution: Mechanism of MSC Differentiation
Chapter 22 - Stem Cells in the Retina: Regenerationand Cell Therapy
22.1 Eye Morphogenes is and Retinogenesis
22.2 Adult Retinal Stem Cells and Neurogenic Potential
22.3 The CM: A Retinal Stem Cell Niche
22.3.1 The CMZ in Cold-Blooded Vertebrates
22.3.2 The CMZ in Birds and Mammals
22.4 The Neurogenic Potential of the RPE
22.4.1 RPE Cell Transdifferentiation in Amphibian and Chick Embryos
22.4.2 RPE Transdifferentiation in Mammals
22.5 The Müller Glial Cells: A Retinal Stem Cells Reservoirin Adulthood?
22.5.2 Amphibians and Birds
22.6 Cell Replacement for Retinal Repair
22.7 Photoreceptors Derived from Human ESand iPS Cells
22.8 RPE Cells Derived from Human ES and iPS Cells
Part 4 - Stem Cell-related Diseases and Therapy Using Stem Cells
Chapter 23 - Leukemic Stem Cells: What the Concept Brings to Disease and Patient Management
23.1.1 Origin of Leukemic Stem Cells
23.1.2 Molecular and Functional Characteristics of LeukemicStem Cells
23.1.3 Identification of Leukemia Stem Cells
23.1.4 Clinical Relevance of Leukemia Initiating Cells
23.1.4.1 Assessment of LSC in patients
23.1.5 Functional Assessment of Mutated Leukemic Clones
23.1.6 Targeting Leukemic Stem Cells
Chapter 24 - Stem Cells for Cardiac Repair
24.1 State of the Art of the Chapter Topic
24.1.1 Acute Myocardial Infarction
24.2 Major Unsolved Problems and OngoingControversies
24.2.1 Choice of the Cells:
24.2.2 Early Postprocedural Cell Retention
24.2.3 Survival of Engrafted Cells
24.2.4 Link of Engraftment to Mechanism of Action of the Cells
24.2.5 Imaging of Stem Cells
24.2.6 Autologous vs Allogeneic Cells
24.2.7 Combination of Biomaterials with Cells
24.3 Contributor’s Group Contributions
24.3.1 Development of Human ESC-Derived Cardiac Progenitors
24.3.2 Method of Delivery
24.3.3 Vascularization of the Graft
Chapter 25 - Stem Cells for Red Blood CellProduction
25.1 A Scientific Challenge
25.2 From the Laboratory to the Clinic
25.3 The Biotechnological Era
25.4 The Obstacles to Overcome
25.5 Technological and Economic Challenges of the LargeScale Production of Red Blood Cells
Chapter 26 - Prospectives for Therapy with Stem Cellsin Skeletal Muscular Diseases
26.1 What is Expected from a Good Cell Candidate?
26.2.1.2 Skeletal muscle aldehyde dehydrogenase-positivecells (SMALD)
26.2.2.1 BMSCs and SP cells
26.2.2.3 Mesoangioblasts/Pericytes
26.3 Therapeutic Application and Future Optimization
Part 5 - Regulatory and Philosophical Aspects
Chapter 27 - Legal Framework for Research on HumanEmbryonic Stem Cells in Franceand in Europe
27.2 How to Regulate hESC Research? the French Example
27.2.1 General Provisions Regarding hESC Research
27.2.2 Agence dela Biomédecine as the Central Piece of the National Regulation
27.2.3 Authorization Delivery
27.2.4 Donation of Human Embryos for Research
27.2.3 Authorization Delivery
27.2.4 Donation of Human Embryos for Research
27.2.5 Translating hESC Research into Clinics
27.3 Examples of Regulations in Europe: France’s Neighbors and Significant Variations in Regulating hESC Research
27.3.1.1 Regulation frame
27.3.1.2 Criteria for authorization
27.3.1.4 Process for approval
27.3.1.5 Embryos for research
27.3.2.1 Regulation frame
27.3.2.3 Process for approval
27.3.2.4 Research using human embryos: license from HFEA
27.3.2.5 Research using established hESC lines: the “steering committee for the UK stem cell bank and for the use of stem cell lines”
27.3.2.6 Embryos for research
27.3.3.1 Regulation frame
27.3.3.3 Process for approval
27.3.3.4 Embryos for research
Chapter 28 - Stem Cell Epistemological Issues
28.1 Self-Renewal and Differentiation: Some Clarifications
28.2 Is It Possible to Distinguish Stem Cells from Non-Stem Cells Through Self-Renewal and Differentiation Abilities?
28.3 Do Stem Cells Belong to a Natural Kind?
28.4 Does the Concept of Stem Cell Refer to “Entities” or to a Cell“ State”?
28.5 Stemness Ontology: Not Two But Four Conceptions of Stemness
28.7 Concluding Perspectives
Chapter 29 - Future Outlook
29.1 The Complexity of Stem Cell Mechanisms
29.2 Origin and Evolution of Stem Cells
29.3 Therapeutic Applications of Stem Cells