This book covers a wide range of topics that illustrate the various functions of autophagy in stem cells and offers insights on the mechanisms by which autophagy can regulate stem-cell self-renewal and facilitate specific differentiation programs. Stem cells are unique cells present in most multicellular animals and are essential for their survival. They have two unique properties: the ability to self-renew and the ability to differentiate into one or more cell types. These characteristics of stem cells have found immense therapeutic potential in regenerative medicine. Autophagy is a crucial membrane trafficking pathway that is essential for maintaining cellular homeostasis that involves sequestration of non-functional proteins, protein aggregates and damaged organelles in double-membraned vesicles called autophagosomes, which are subsequently targeted to the lysosome for degradation. The primary aim of this book is to provide knowledge of recent developments in our understanding of the role of autophagy in stem cells, including germline stem cells.
Autophagy is considered a promising target for many diseases. Significant efforts are being developed to identify specific modulators of autophagy, which will aid in designing combinatorial therapeutic strategies that will allow significant improvements in regenerative medicine.
Author(s): Bhupendra V. Shravage, Kursad Turksen
Series: Stem Cell Biology and Regenerative Medicine, 73
Publisher: Springer
Year: 2022
Language: English
Pages: 289
City: Cham
Preface
Contents
1 Assays for Monitoring Autophagy in Stem Cells
Introduction
Autophagy Process and Mechanism
Techniques for Assessing Autophagy Orchestration
Electron Microscopy Imaging
Fluorescence Microscopy
LC3 Antibody Tagging
Fluorescent Protein Tagging of LC3
mRFP/mCherry-GFP-LC3 Tandem Reporter Constructs and Their Advancements
GFP-LC3-RFP-LC3∆G
SQSTM/p62/Ref(2)P Tagging
Evaluation of Specific Steps During Autophagy
Autophagy Visualization Dyes
Tracking Mitophagy in Stem Cells
Atg8s/LC3 and p62 Protein Expression in Stem Cells
LC3 Turnover Assays
Flow Cytometry and Fluorescence-Associated Cell Sorting (FACS)
Potential Probes for Monitoring Autophagy
Gene Expression Assays
Protein Interaction Databases
Conclusion
References
2 Autophagy in Stem Cell Maintenance and Differentiation
Introduction
Autophagy Compared to Necrosis and Apoptosis
The Autophagic Cascade
Types of Autophagy
Role of Autophagy in Stem Cell Maintenance
Role of Autophagy in Maintenance of Hematopoietic Stem Cells (HSCs)
Role of Autophagy in Maintenance of Neural Stem Cells
Role of Autophagy in Maintenance of Muscle Stem Cells
Role of Autophagy in Maintenance of Bone Marrow Derived Mesenchymal Stem Cells (BMSCs)
Role of Autophagy in Maintenance of Hepatic Progenitor Cells
Role of Autophagy in Maintenance of Intestinal Stem Cells (ISCs)
Autophagy and Stem Cell Differentiation
Role of Autophagy in the Differentiation of HSCs
Role of Autophagy in the Differentiation of NSCs
Role of Autophagy in the Differentiation of Cardiac Stem Cells
Role of Autophagy in Adipocyte Formation from MSCs
Role of Autophagy in Osteoclastogenesis
Role of Autophagy During Embryogenesis
Conclusion
References
3 Autophagy in Embryonic Stem Cells and Neural Stem Cells
Introduction
Embryonic Stem Cells
Autophagy in ESCs and During Embryogenesis: Evidence and Importance
Specific Roles of Autophagy in ESCs
Autophagy and Proteostasis in ESCs
Autophagy and Pluripotency Factor Turnover
Mitophagy in ESCs
Midbody Ring, Autophagy, and ESCs
Regulation of Autophagy in ESCs
Autophagy and Neural Stem Cells
Neural Stem Cells
Evidence for Autophagy in Neural Stem Cells
Implications of Autophagy Defects in Development and Disease
Conclusions and Outlook
References
4 Autophagy in Germline Stem Cells
Overview of Autophagy
Overview of GSCs in Model Organisms
Perturbed Autophagy Affects Fertility
Autophagy and Signaling in GSCs
Autophagy, Lipid Metabolism, and Germline Stem Cells
Autophagy and Organelle Homeostasis in GSCs
Autophagy in Programmed Cell Death and Germline Development
Conclusions
References
5 The Role of Autophagy in the Regulation of Hematopoietic Stem Cells
Introduction
Autophagy
Types of Autophagy
Microautophagy
Chaperone-Mediated Autophagy (CMA)
Macroautophagy
Autophagy and Stem Cells
Hematopoietic Stem Cells
Neural Stem Cells
Muscle Stem Cells
Induced Pluripotent Stem Cells
Cancer Stem Cells
Autophagy and Hematopoiesis
Hematopoiesis
Role of Autophagy in the Ontogeny of the Hematopoietic System
Role of Autophagy in Hematopoietic Stem Cell Fates
Autophagy in HSC Quiescence
Autophagy in HSC Self-renewal
Autophagy in HSC Differentiation
Role of Autophagy in HSC Aging
Role of Autophagy in Niche-Mediated Regulation of Hematopoietic Stem Cells
Role of Autophagy in Hematological Disorders
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Chronic Myeloid Leukemia (CML)
Lymphoid Malignancies
Final Remarks
References
6 Autophagy in Muscle Stem Cells
Introduction
Skeletal Muscle Architecture
Satellite Cells: Muscle-Resident Stem Cells
The Role of Satellite Cells
Myogenesis: Quiescence, Activation, Proliferation, Differentiation, and Self-renewal
Satellite Cells Contribute to Muscle Health
Autophagy in Skeletal Muscle
Basal Autophagy is Required to Maintain Muscle Mass
Role of Selective Autophagy in Muscle Homeostasis
Autophagy in Muscle Regeneration and Exercise
Autophagy in Muscle Health
Autophagy in Muscle Stem Cells
Homeostatic Maintenance of Muscle Stem Cells
Autophagy in Satellite Cells is Under Circadian Regulation
Quiescent Satellite Cells Exist in Two Distinct Metabolic States
Contribution of Autophagy in Satellite Cell Activation
Autophagy Prevents Apoptosis in Satellite Cells
Satellite Cell Function and Regenerative Capacity
The Role of mTOR Signaling in Myogenesis
Coordination of Myogenic Differentiation and p53-Dependent Autophagy
Mitophagy is Required for Mitochondrial Biogenesis and Myogenesis
Conclusion
References
7 Autophagy in the Intestinal Stem Cells
Introduction
The Role of Autophagy in Intestinal Stem Cell Maintenance and Proliferation
Role of Autophagy in Intestinal Stem Cell Differentiation
Insects as Model Organisms in Autophagy Studies in Intestinal Stem Cells
Pathologies Associated with Autophagy in Intestinal Stem Cells
Concluding Remarks
References
8 The Autophagy Lysosomal Pathway: Friend or Foe in Adult Neural Stem Cells?
Introduction
Neural Stem Cells and Neurogenesis in the Adult Mammalian Brain
Adult Neural Stem Cell Niches and the Neurogenic Cascade
The Quiescent State of Adult Neural Stem Cells
Autophagy, Neural Stem Cells and Adult Neurogenesis
The Autophagy Lysosomal Pathway in the Adult Neurogenic Niches
The Autophagy Lysosomal Pathway in Adult NSC Quiescence
The Autophagy Lysosomal Pathway in the Autophagic Cell Death of Adult NSCs
Concluding Remarks
References
9 Autophagy in Mesenchymal Stem Cell-Based Therapy
Introduction
Autophagy-An Intracellular Mechanism for the Restoration of Cell Energy
Autophagy-Dependent Regulation of Stemness and Differentiation Potential of MSCs
Activation of Autophagy as New Approach for Attenuating Apoptosis of Transplanted MSCs
MSCs Modulate Autophagy in Parenchymal and Immune Cells Affecting Progression of Degenerative and Inflammatory Diseases
Modulation of Autophagy as New Approach for Enhancement of MSCs’ Immunosuppressive Properties
Autophagy Improves the Pro-angiogenic Properties of MSCs
Conclusions
References
10 Autophagic Control of Stem Cells Differentiation into Osteogenic Lineage—Implications in Bone Disorders
Introduction
Autophagic Regulation of Embryonic Development
Autophagy During Embryogenesis
Autophagy in ESCs
Autophagy in Skeletogenesis
Regulation of Stem Cells Characteristics by Autophagy
Autophagy in Differentiation Fate of Stem Cells
Autophagic Regulation of Osteogenic Differentiation of Stem Cells
Implications in Bone Disorders
Autophagic Dysregulation in Osteoporosis
Autophagic Dysregulation in Arthritis
Conclusion and Final Remarks
References
11 Autophagy in Cancer Metastasis
Introduction
Cancer Metastasis
Invasion and Migration
Intravasation
Survival in the Circulation
Extravasation
Colonization
Autophagy in Cancer Metastasis
Role of Autophagy in Regulating EMT
Autophagy In Inducing Resistance To Anoikis
Role of Autophagy in Governing Tumour Cell Motility
Autophagy in Regulating Tumour Cell Dormancy and Therapy Resistance
Involvement of Autophagy During Tumour Immune Surveillance
Role of Autophagy in Other Tumour Microenvironment Activities
Autophagy in Cancer Therapeutics
Summary
References
Index
