Proteoglycans in Stem Cells: From Development to Cancer

Preface
Contents
About the Editors
Chapter 1: Heparan Sulfate Proteoglycans in the Stem Cell Niche: Lessons from Drosophila
	1.1 Introduction
	1.2 Heparan Sulfate Proteoglycans Regulate Stem Cell Number in the Drosophila Germline Stem Cell Niche
		1.2.1 The Drosophila Female Germline Stem Cell Niche in the Ovary
		1.2.2 Dally Regulates Stem Cell Number in the GSC Niche
		1.2.3 The Drosophila Male Germline Stem Cell Niche in the Testis
		1.2.4 HS in the Niche Regulates GSC Asymmetric Division
		1.2.5 HS in the Niche Prevents Tumor Formation in the Testis
	1.3 Heparan Sulfate Proteoglycans Regulate Stem Cell Replacement in the Drosophila Follicle Stem Cell Niche
		1.3.1 The Drosophila Ovarian Follicle Stem Cell Niche and Stem Cell Quality Control
		1.3.2 Glypicans Regulate Follicle Stem Cell Competition
	1.4 Heparan Sulfate Proteoglycans Regulate Stem Cell Activity in the Drosophila Midgut
		1.4.1 The Drosophila Midgut Intestinal Stem Cells
		1.4.2 HSPGs Regulate Damage-Induced Activation of ISCs
		1.4.3 Sulf1 Is Required for ISC Inactivation at Late Stages of Regeneration
	1.5 Concluding Remarks
	References
Chapter 2: Proteoglycans in Zebrafish Development
	2.1 Studying Development in Zebrafish
	2.2 Loss of Gene Function Experiments in Zebrafish
	2.3 Glycosaminoglycan Biosynthesis
	2.4 Structure and Amounts of HS and CS/DS During Zebrafish Development
	2.5 Maternal Contribution
	2.6 Craniofacial Phenotypes
	2.7 Phenotypes Associated with Altered HS Production
	2.8 Morpholino Studies
	2.9 Genetic Mutants in CS/DS Biosynthesis Remain to Be Described
	2.10 Hyaluronan
	2.11 Concluding Remarks
	References
Chapter 3: The Pivotal Role of Versican Turnover by ADAMTS Proteases in Mammalian Reproduction and Development
	3.1 The Provisional Extracellular Matrix of the Mammalian Embryo
	3.2 Overview of the ADAMTS Proteases and Versican
	3.3 Versican Turnover During Ovulation and Role of ADAMTS Proteases in Fertility
	3.4 ADAMTS9 Is Essential for Myometrial Activation and Parturition
	3.5 ADAMTS Proteolysis of Versican in the Maternal-Fetal Interface
	3.6 ADAMTS Proteolysis of Versican During Morphogenesis
	3.7 Summary
	References
Chapter 4: Use of Chondroitin Sulphate to Aid In Vitro Stem Cell Differentiation
	4.1 Introduction
	4.2 CS Sulphation Motifs Regulate Cell Behaviour, Can They Be Used to Promote Tissue Repair?
		4.2.1 Evolution of GAGs as Cellular Mediator Molecules
		4.2.2 GAG Sulphation Motifs as Molecular Recognition and Information Transfer Motifs Which Direct Cellular Behaviour
	4.3 Stem Cells Are Responsive to Biomechanical Stimuli from the ECM
	4.4 Phylogenetic Conservation of GAG Structure in Vertebrate and Invertebrate Evolution
	4.5 CS Sulphation Motifs Identified by Antibodies 4-C-3, 7-D-4 and 3-B-3(-)
		4.5.1 Identification of the CS Hydrolase: ``the Mammalian Chondroitinase´´ as the Generator of the 3-B-3(-) and 2-B-6(-) CS Su...
	4.6 GAGs and Tissue Repair: GAG Bioscaffolds Which Promote Stem Cell Differentiation
		4.6.1 Prospective Roles for Biglycan, Decorin and FGF-18 in Osteogenesis
			4.6.1.1 Biglycan and Decorin, Modulate Bone Marrow Stromal Cell Differentiation, Co-ordinate TGF-β Sequestration in the ECM an...
	4.7 FGF-18 Induces Osteogenic Differentiation of Chondrocytes and CS Sulfation Motif Expression by Osteoprogenitor Stem Cells ...
		4.7.1 FGF-18 Induces Expression of Specific CS Sulfation Motifs by Osteoprogenitor Cells
		4.7.2 Modulation of Stem Cell Activity by Extrinsic Forces
	4.8 CS Bioscaffolds and Their Instructional Properties Over MSC Differentiation
	4.9 Expression of the 7-D-4, 3-B-3(-) and 4-C-3 CS Sulphation Motifs Are Upregulated During Osteogenic Differentiation and Sti...
	4.10 Concluding Remarks
	References
Chapter 5: Regulatory Functions of Heparan Sulfate in Stem Cell Self-Renewal and Differentiation
	5.1 Introduction
	5.2 Heparan Sulfate
	5.3 Heparan Sulfate Expression During Embryonic Stem Cell Self-Renewal and Differentiation
	5.4 Heparan Sulfate Regulates ESC Self-Renewal and Related Signaling
	5.5 Heparan Sulfate Regulates Embryonic Stem Cell Differentiation and Related Signaling
	5.6 Heparan Sulfate Regulates Neural Progenitor Stem Cell Differentiation and Related Signaling
	5.7 Heparan Sulfate Regulates Prostate Development and Prostate Stem Cell Activity
	5.8 Conclusions and Perspectives
	References
Chapter 6: Proteoglycans, Neurogenesis and Stem Cell Differentiation
	6.1 Proteoglycans
	6.2 Neurogenesis
		6.2.1 Human Embryonic Neurogenesis
		6.2.2 Adult Human Neurogenesis
		6.2.3 Understanding Human Neurogenesis: Evidence from Murine and Other Models
	6.3 Neural Cell Types
		6.3.1 Neurons
		6.3.2 Glial Cells: Astrocytes and Oligodendrocytes
			6.3.2.1 Astrocytes
			6.3.2.2 Oligodendrocytes
	6.4 The Neural Stem Cell Niche
		6.4.1 The Extracellular Matrix (ECM) and Cellular Components of the NSC Niche
		6.4.2 ECM Proteins in NSC Regulation
	6.5 HSPG Mediated Signalling in the Neural Niche
		6.5.1 FGF-2 and EGF
		6.5.2 Wnt/β-Catenin Pathway
		6.5.3 Sonic Hedgehog (Shh) Pathway
		6.5.4 Other Signalling Pathways
		6.5.5 Platelet-Derived Growth Factor (PDGF)
	6.6 HSPGs in Neural Development
		6.6.1 SDCs and Neurogenesis
		6.6.2 GPCs and Neurogenesis
		6.6.3 Matrix Localised Perlecan
	6.7 Stem Cell Classification
		6.7.1 Neural Stem Cell Characterisation
		6.7.2 Neural Stem Cell Expansion and Derivation
		6.7.3 Neurosphere Assay
		6.7.4 Adherent Monolayer
	6.8 Models of Human Neurogenesis
		6.8.1 Embryonic Stem Cell-Derived NSCs
		6.8.2 Induced Pluripotent Stem Cell (iPSC) Derived NSCs
	6.9 Human Mesenchymal Stem Cells
		6.9.1 Isolation
		6.9.2 Characterisation
		6.9.3 Expansion
		6.9.4 Differentiation
		6.9.5 hMSC-Induced Neurosphere Formation Versus Terminal Differentiation
	6.10 Where to Next?
		6.10.1 Heparan Sulfate PGs and Neural Stem Cells: A Target for Therapy?
		6.10.2 Approaches for Exploiting HSPGs as Therapeutic Targets
	6.11 Conclusion
	References
Chapter 7: Syndecan-3: A Signaling Conductor in the Musculoskeletal System
	7.1 Introduction
	7.2 Syndecans
		7.2.1 Syndecan Structure
		7.2.2 Syndecan Functions
	7.3 Syndecan-3
	7.4 Syndecan-3 in the Musculoskeletal System
		7.4.1 SDC3 in Muscle Development
		7.4.2 SDC3 in Muscle Regeneration, Aging, and Disease
		7.4.3 SDC3 in Cartilage Development, Regeneration, and Disease
		7.4.4 SDC3 in Osteogenesis
		7.4.5 Concluding Remarks
	References
Chapter 8: Proteoglycans of the Neural Stem Cell Niche
	8.1 Stem Cells in the Developing and Adult CNS
	8.2 The Neural Extracellular Matrix
	8.3 The Stem Cell Niche
	8.4 ECM of the Niche
	8.5 The GAG-Chains of Proteoglycans
	8.6 Heparan Sulfate GAGs
	8.7 Heparan Sulfate Proteoglycans
	8.8 Chondroitin Sulfate GAGs and CSPGs
	8.9 Discrete CS-GAG Structures
		8.9.1 The DSD-1-Epitope
		8.9.2 RPTP-zeta and Phosphacan
		8.9.3 Lecticans
		8.9.4 NG2/CSPG4
	8.10 Complex Glycans
	8.11 Glioblastoma Stem Cells
	8.12 Proteoglycans in GBM
	8.13 Concluding Remarks
	References
Chapter 9: Heparan Sulfate in Normal and Cancer Stem Cells of the Brain
	9.1 Neural Stem Cells and Brain Tumor Stem Cells
	9.2 Introduction to the Extracellular Matrix in Neural Stem Cells and Brain Tumors
	9.3 Extracellular Matrix Organization in the Brain
	9.4 Heparan Sulfate Proteoglycans and Their Biosynthesis, Modification and Degradation
	9.5 Heparan Sulfate in Neural Stem Cell Commitment and Differentiation
	9.6 Consequences for Brain Development When Heparan Sulfate Is Not Functional
	9.7 Glioblastoma
	9.8 Medulloblastoma
	9.9 Cancer Stem Cells Models of Malignant Brain Tumors
	9.10 Heparan Sulfate in Brain Tumors and Brain Tumor Stem Cells
	9.11 Concluding Remarks
	References
Chapter 10: The Hyaluronic Acid-CD44 Interaction in the Physio- and Pathological Stem Cell Niche
	10.1 Introduction
	10.2 The Stem Cell Niche: Types of Niche and ECM Aspects
		10.2.1 Different Stem Cell Niches
	10.3 CD44: The Stem Cell Marker and the Main Hyaluronan Receptor
		10.3.1 Structure: Exon Composition and Functional Domains
		10.3.2 Hyaluronan
	10.4 CD44-HA Interaction in the Stromal Cell from the Stem Cell Niche
		10.4.1 Biological Functions of CD44 Associated with Stemness Properties in the Niche
		10.4.2 CD44 as an ECM Molecules-Binding Protein
		10.4.3 CD44 as a Cell Surface Co-receptor
		10.4.4 CD44 as a Modulator of ABC Transporter Function
		10.4.5 CD44 as a Modulator of Hypoxia
		10.4.6 CD44 as a Modulator of Migration and Anchorage
		10.4.7 CD44 as a Modulator of Quiescence
		10.4.8 Cellular Components of the Niche Stroma
			10.4.8.1 MSCs
			10.4.8.2 Immune Cells
	10.5 CD44-HA Interaction in Tumor Transformation
	10.6 Conclusion
	References
Chapter 11: Proteoglycans in Glioma Stem Cells
	11.1 Introduction
	11.2 Proteoglycan Family Members and Protein Structure
	11.3 Gliomas
	11.4 Proteoglycan Functions in Glioma
	11.5 Proteoglycan Functions in Glioma Stem Cells
	11.6 Proteoglycans as Therapeutic Targets in Glioma
	11.7 Summary and Conclusions
	References
Chapter 12: Role of Syndecan-1 in Cancer Stem Cells
	12.1 The Cancer Stem Cell Hypothesis
	12.2 Cell-Surface Heparan Sulfate: A Versatile Integrator of Stemness-Related Signaling Events
		12.2.1 Wnt Signaling
		12.2.2 The Hedgehog Pathway
		12.2.3 Notch Signaling
		12.2.4 FGF Signaling
		12.2.5 The NF-κB/IL-6/JAK/STAT3-Signaling Axis
	12.3 Syndecan-1: A Modulator of Cancer Stem Cell Function
	12.4 Conclusions and Perspective
	References