Hair Cell Regeneration

The Acoustical Society of America
Series Preface
Preface 1992
Volume Preface
Contents
Contributors
Chapter 1: Sensory Regeneration in the Inner Ear: History, Strategies, and Prospects
1.1 Introduction
1.2 Historical Overview of Otic Regeneration
1.2.1 Postnatal Generation of Sensory Receptors in Vertebrates
1.2.2 Postnatal Addition of Hair Cells in Cold-Blooded Vertebrates
1.2.3 Sensory Regeneration in the Avian Inner Ear
1.3 Overview of Contents
1.4 Conclusions
References
Chapter 2: Nonmammalian Hair Cell Regeneration: Cellular Mechanisms of Morphological and Functional Recovery
2.1 Introduction
2.2 Nonmammalian Hair Cell Regeneration: An Overview
2.3 Supporting Cell Populations and Their Functions During Regeneration
2.3.1 Identities and Locations of Hair Cell Progenitors in Fish
2.3.2 The Role of Peripheral Supporting Cells in Fish
2.3.3 Supporting Cell Diversity in Birds
2.4 Approaches to Define New Molecular Regulators Using Nonmammals
2.4.1 Transcriptional Profiling
2.4.2 Genetic and Molecular Screening
2.5 Molecular Regulation of Supporting Cells
2.5.1 Transcription Factors Regulate Hair Cell Regeneration in Nonmammals
2.5.2 Cell-Cell Signaling Molecules That Regulate Hair Cell Regeneration in Birds and Fish
2.5.2.1 Notch Signaling
2.5.2.2 Wnt Signaling
2.5.2.3 Other Signaling Pathways
2.5.3 Epigenetic Mechanisms Controlling Nonmammalian Hair Cell Regeneration
2.6 Conclusion
References
Chapter 3: Cell Junctions and the Mechanics of Hair Cell Regeneration
3.1 Introduction
3.2 Shape Change Controls Proliferation of Supporting Cells
3.3 Actomyosin Contractility at Apical Junctions Accelerates Wound Closure in the Lesioned Vestibular Epithelium
3.4 Maturational Reinforcement of Adherens Junctions Coincides with Age-Related Declines in the Plasticity of Mammalian Supporting Cells
3.4.1 The Unique Circumferential F-actin Bands in Mammalian Supporting Cells
3.4.2 Potential Mechanical Influence of the Thick F-actin Bands that Develop in Mammalian Supporting Cells
3.4.3 Structure and Regulation of the Circumferential F-actin Bands in Supporting Cells
3.4.3.1 Sarcomeric Actomyosin Network at Cochlear Apical Junctions
3.4.3.2 Regulation of the Circumferential F-actin Bands by Rho GTPases
3.5 E-cadherin Accumulates at Supporting Cell Junctions in the Mammalian Vestibular Epithelium
3.5.1 Hypothesized Role for N-cadherin in Limiting Supporting Cell Proliferation
3.5.2 A Special Case: Apical Junctions in the Anolis Lizard
3.6 Regulation and Perturbation of Apical Junctions in Mammalian Supporting Cells
3.6.1 Potential Interaction of Notch Signaling and E-cadherin Adhesion
3.7 Intracellular Signaling Downstream of Mechanical Signals
3.7.1 YAP/TAZ and the Hippo Pathway
3.7.1.1 YAP-TEAD Regulate Cell Cycle Arrest and Size Control in Hair Cell Epithelia
3.7.1.2 YAP-TEAD Signaling in Repair and Regeneration
3.7.2 Canonical Wnt Signaling
3.8 Supporting Cell-Extracellular Matrix Interactions
3.9 Summary
3.9.1 A Hypothetical Model for Mechanical Control of Hair Cell Replacement
3.9.2 Outstanding Questions and Opportunities
3.10 Conclusions
References
Chapter 4: Mammalian Hair Cell Regeneration
4.1 Introduction
4.2 Structural and Developmental Considerations
4.2.1 Structure of the Mammalian Vestibular Sensory Epithelia
4.2.2 Development of the Vestibular Sensory Epithelia
4.2.3 Structure of the Mammalian Auditory Epithelium, the Organ of Corti
4.2.3.1 Hair Cell Types
4.2.3.2 Supporting Cells
4.2.3.3 Features of Organ of Corti Development
4.3 Hair Cell Generation and Regeneration in the Immature Inner Ear
4.3.1 Generation of Supernumerary Hair Cells
4.3.2 Hair Cell Regeneration in the Immature Inner Ear
4.3.3 Stem Cells in the Sensory Epithelia
4.4 Hair Cell Generation and Regeneration in the Mature Vestibular Sensory Epithelia
4.4.1 Characteristics of Spontaneous Regeneration in Adult Mammalian Utricles
4.4.2 Origin of Regenerated Hair Cells
4.4.3 Functionality of Regenerated Vestibular Hair Cells
4.5 Enhancing Hair Cell Regeneration by Phenotypic Conversion in Mature Animals
4.5.1 Vestibular Sensory Epithelia
4.5.1.1 Notch Pathway Inhibition
4.5.1.2 Overexpression of Atoh1
4.5.2 Inducing Hair Cell Regeneration in the Mature Organ of Corti in Vivo
4.5.2.1 Overexpression of Atoh1
4.5.2.2 Notch Pathway Inhibition
4.5.3 Additional Factors to Promote Differentiation of Regenerated Hair Cells
4.5.4 Clinical Trials
4.6 Regeneration of Vestibular Hair Cells: Summary
4.7 Cochlear Cellular Pathology and Challenges to Hair Cell Regeneration and Recovery of Auditory Function
References
Chapter 5: Specification and Plasticity of Mammalian Cochlear Hair Cell Progenitors
5.1 Introduction
5.2 Induction of the Inner Ear and the Development of Prosensory Patches
5.3 Regulation and Function of the Atoh1 Transcription Factor During HC Development
5.4 Promotion of Supporting Cell Fate Through Notch-Mediated Lateral Inhibition from Hair Cells
5.5 Regulation of Supporting Cell Fate Decisions: Extracellular Signals and Intracellular Transcription Factors
5.6 Toward Hair Cell Regeneration: Lessons from Non-mammalian Models and Neonatal Mice
5.7 Enhancing Mammalian Hair Cell Regeneration: Reprogramming of Supporting Cells into Hair Cells
5.8 Epigenetic Regulation of Gene Expression in the Cochlea
5.9 Summary
References
Chapter 6: Inner Ear Cells from Stem Cells: A Path Towards Inner Ear Cell Regeneration
6.1 Introduction
6.1.1 Pluripotent Stem Cells
6.2 Two-Dimensional Culture Systems
6.2.1 Inner Ear Replacement Parts and Hair Cells from Scratch
6.2.2 Hair Cell-Like Cells from Pluripotent Stem Cells
6.2.3 Limitations of Two-Dimensional Culture Systems
6.3 Three-Dimensional Culture and Organoids
6.3.1 Derivation of Inner Ear Organoids
6.3.2 Limitations of Three-Dimensional Culture Systems
6.4 Stem Cells in the Adult Inner Ear
6.4.1 Stem Cells Are the Source of the Strong Regenerative Capacity of the Avian Inner Ear
6.4.2 Stem Cells in the Inner Ear of Adult Rodents Are Restricted to the Vestibular System
6.5 Stem Cells in the Neonatal Rodent Cochlea
6.5.1 Supporting Cells of the Neonatal Organ of Corti Display Stem Cell-Like Capacity
6.5.2 Proliferation of Dissociated Neonatal Organ of Corti Supporting Cells Can be Manipulated with Growth Factors and Small Molecules
6.6 Emerging New Methods Towards Hair Cell Regeneration
6.6.1 CRISPR Genome Editing to Enhance Stem Cell Applications?
6.6.2 Supporting Cell Reprogramming
6.7 Conclusion
References
Chapter 7: Spiral Ganglion Neuron Regeneration in the Cochlea: Regeneration of Synapses, Axons, and Cells
7.1 Introduction to Spiral Ganglion Neurons
7.1.1 Peripheral Connections of Spiral Ganglion Neurons
7.1.2 Glia and Myelination
7.1.3 Central Connections of SGNs
7.1.4 Neurotrophic Factors
7.2 Synaptopathy and Synapse Regeneration
7.2.1 Primary Degeneration
7.2.2 Secondary SGN Degeneration After Hair Cell Loss
7.3 Regeneration of SGN Axons and Guidance of Their Growth
7.3.1 Stimulation of Growth by Neurotrophic Factors
7.3.2 Intracellular Signaling for Neurite Growth/Retraction
7.3.3 Directional Guidance by Neurotrophic Factors
7.3.4 Directional Guidance by Substrate Pattern/Materials
7.4 Cochlear Implants Present a Model for SGN Regeneration
7.4.1 Cochlear Implants Depend on SGN Health
7.4.2 Cochlear Trauma and Inflammation Likely Reduce SGN Health and CI Performance
7.5 Regeneration of SGNs from Stem Cells
7.5.1 Assessments of Success
References
Chapter 8: Genetic and Epigenetic Strategies for Promoting Hair Cell Regeneration in the Mature Mammalian Inner Ear
8.1 Introduction
8.2 Mouse Models for Altering Gene Expression
8.2.1 Cre/lox Technology
8.2.1.1 Cell Type-Specific and Temporal Control of Recombination
8.2.1.2 Generation of Cre and CreERT Mouse Lines
8.2.1.3 Characterizing Cre/CreERT Expression
8.2.1.4 Interpreting Cre/CreERT Reporter Expression
8.2.1.5 Cre/CreERT Efficiency
8.2.1.6 Caveats for Cre/CreERT Studies
8.2.2 CreERT Alleles Expressed in Supporting Cells
8.2.2.1 CreERT Alleles for Adult Auditory Supporting Cells
8.2.2.2 CreERT Alleles for Adult Vestibular Supporting Cells
8.2.3 Tetracycline-Responsive Gene Regulation
8.2.4 CRISPR/Cas Approaches
8.2.4.1 Generation of Knockout Mice
8.2.4.2 Advantages Over Conventional Mouse Mutagenesis
8.2.4.3 Genetic Knock-In Using CRISPR/Cas
8.2.4.4 Cas9-Expressing Mouse Lines
8.2.4.5 Reducing Off-Target Effects
8.2.4.6 DNA Base Editing with Dead Cas9
8.3 Targeting Epigenetic Processes for Hair Cell Regeneration
8.4 Virus-Mediated Gene Transfer in Adult Supporting Cells
8.4.1 Introduction to Adeno-Associated Virus
8.4.1.1 AAV Infection and Tropism
8.4.1.2 Recombinant Adeno-Associated Viral Vectors
Capsid Discovery to Achieve Novel Transduction
8.4.1.3 Packaging Capacity
8.4.2 Gain of Function in Supporting Cells
8.4.2.1 Supporting Cell Transduction Efficiency
8.5 Loss of Function in Supporting Cells
8.5.1 MicroRNAs and Small Interfering Ribonucleic Acids
8.5.2 Antisense Oligonucleotides
8.6 Summary: Refocusing Hair Cell Regeneration Model Systems
References