Hematopoietic Stem Cells: Keystone of Tissue Development and Regenerative Medicine (Advances in Experimental Medicine and Biology, 1442)

Foreword 1
Foreword 2
Preface
Contents
About the Editors
1: Hematopoietic Stem Cell Development in Mammalian Embryos
	1.1 Endothelial Origin and Functional Heterogeneity of Emerging HSCs in Mouse Embryos
	1.2 HSC-Dependent and HSC-Independent Origin of Lymphopoiesis and Myelopoiesis
	1.3 Epigenetic Regulation of HSC Formation
	1.4 EHT and the Generation of Human HSCs
	1.5 Development of Multiple Hematopoietic Lineages in Human Embryos
	References
2: Hematopoietic Stem Cells and Their Bone Marrow Niches
	2.1 The HSC Niche Concept
	2.2 The Heterogeneity of HSCs and Their Niches
	2.3 The Regulation of HSCs by Bone Marrow Niche Cells
	2.4 The Aging Bone Marrow Niche
	2.5 Bone Marrow Niche for Leukemia
	2.6 Future Perspectives
	References
3: Emerging Roles of Epigenetic Regulators in Maintaining Hematopoietic Stem Cell Homeostasis
	3.1 Introduction
	3.2 DNA Modification
	3.3 Histone Modifications
		3.3.1 Histone Methylation
		3.3.2 Histone Acetylation
		3.3.3 Histone Ubiquitination
	3.4 Spatial Organization of Chromosomes
	3.5 Noncoding RNAs (ncRNAs)
		3.5.1 MiRNAs
		3.5.2 LncRNAs
	3.6 RNA Modification
		3.6.1 m6A Modification
		3.6.2 A-to-I Editing
	3.7 Conclusion
	References
4: Metabolism in Hematopoiesis and Its Malignancy
	4.1 Introduction
	4.2 Glucose Flux Through Glycolysis and Pentose Phosphate Pathway
		4.2.1 Glucose Metabolism in Normal Hematopoiesis
		4.2.2 Glucose Addiction in Leukemias
	4.3 Amino Acid Metabolism
		4.3.1 Amino Acids Regulate Normal Hematopoiesis
		4.3.2 Leukemia Cells Reprogram Amino Acid Metabolism
	4.4 Fatty Acid Metabolism
		4.4.1 Fatty Acid in Normal Hematopoiesis
		4.4.2 Fatty Acid in Leukemias
	4.5 Nucleotide Biosynthesis
		4.5.1 Nucleotide Biosynthesis in Hematopoiesis
		4.5.2 Nucleotide Biosynthesis in Leukemias
	4.6 Conclusion
	References
5: The Origin of Clonal Hematopoiesis and Its Implication in Human Diseases
	5.1 Introduction
	5.2 Examination of CH by XCI
	5.3 Detection of CH in the Era of Next-Generation Sequencing
	5.4 CH Associated with Leukemia Driver Mutations
	5.5 CH with Non-leukemia Driver Mutations
	5.6 CH Associated with Mosaic Chromosomal Alterations
	5.7 Co-occurrence of CHIP Mutations and mCAs in CH
	5.8 Inherited Risk Factors for SNV/Indel- and mCA-Associated CH
	5.9 Impact of CH-Related SNVs and mCAs on Clonal Outgrowth
	5.10 Epigenetic Regulators
	5.11 Splicing Factors
	5.12 DNA Damage Response Factors
	5.13 CHIP Mutations in Non-cancer Driver Genes
	5.14 mCA
	5.15 Cellular Origins of Expanded Clones in CHIP
	5.16 Impact of Extrinsic Factors on Clonal Outgrowth
	5.17 Association of CH with Hematological Malignancies
	5.18 Functions of CH-Related Mutations in Immune Cells
	5.19 Association of CH with Nonmalignant Diseases
	5.20 Perspective
	References
6: Ex Vivo Expansion and Homing of Human Cord Blood Hematopoietic Stem Cells
	6.1 Introduction
	6.2 Ex Vivo Expansion of CB HSC
		6.2.1 Cytokine-Induced Expansion of CB HSCs
		6.2.2 Expansion of CB HSCs by Targeting Classical Cell Signal Transduction Pathways
		6.2.3 Stromal Cell-Based Expansion of CB HSC
		6.2.4 Small Molecule-Induced Expansion of CB HSCs
		6.2.5 Expansion of CB HSCs by Manipulating Specific Genes Involved in Self-Renewal
		6.2.6 Opportunities and Challenges for CB HSC Expansion
	6.3 Regulation of HSC Homing
		6.3.1 Strategies to Enhance CB HSC Homing
			6.3.1.1 Enhancing CB HSC Homing by Targeting Components on the Cell Surface
			6.3.1.2 Enhancing CB HSC Homing by Targeting Factors in the Cytoplasm
			6.3.1.3 Enhancing CB HSC Homing by Targeting Components in the Nucleus
		6.3.2 Opportunities and Challenges for HSC Homing
	References
7: N6-Methyladenosine RNA Modification in Normal and Malignant Hematopoiesis
	7.1 Introduction
	7.2 Regulators of m6A Modification
	7.3 m6A Modification in Normal Hematopoiesis
		7.3.1 METTL3
		7.3.2 METTL14
		7.3.3 RBM15
		7.3.4 ALKBH5
		7.3.5 YTHDF2
		7.3.6 YTHDC1
	7.4 m6A Modification in Malignant Hematopoiesis
		7.4.1 Acute Myeloid Leukemia (AML)
		7.4.2 Acute Lymphoblastic (or Lymphocytic) Leukemia (ALL)
		7.4.3 Chronic Myeloid Leukemia (CML)
		7.4.4 Lymphoma
		7.4.5 Multiple Myeloma (MM)
	7.5 Targeting of m6A Modification in Malignant Hematopoiesis
	7.6 Conclusions and Perspectives
	References
8: Immune System Influence on Hematopoietic Stem Cells and Leukemia Development
	8.1 The Stem Cell Milieu
		8.1.1 Stem Cells as Architects of Their Own Niche
		8.1.2 Intrinsic Stem Cell Mechanisms of Immunomodulation
	8.2 Distinctive Immunogenicity of Stem Cells
		8.2.1 Stem Cell Immune Privilege
		8.2.2 Extrinsic Stem Cell Mechanisms of Immunomodulation
	8.3 Immunosurveillance and Leukemia Initiation
	8.4 Conclusions and Future Directions
	References
9: Learning from Zebrafish Hematopoiesis
	9.1 Unique Advantages of Zebrafish for the Research of Hematopoiesis
	9.2 Initiation of the Primitive Hematopoiesis in Zebrafish
	9.3 The Emergence of the Definitive Hematopoiesis in Zebrafish
	9.4 Hematopoietic Niches in Zebrafish
	9.5 Forward and Reverse Genetic Studies of Zebrafish Hematopoiesis
	9.6 Zebrafish Models of Human Hematopoietic Disorders and Drug Discovery
	9.7 Conclusions and Perspective
	References
10: Multi-lineage Differentiation from Hematopoietic Stem Cells
	10.1 Introduction
	10.2 Regulatory Networks of Lineage Commitment
		10.2.1 Transcription Factors
		10.2.2 Epigenetic Programming
		10.2.3 Other Layers of Gene Regulation
	10.3 Evolving Models of Hematopoietic Hierarchy
		10.3.1 Heterogeneous in Hematopoietic Cell Population
		10.3.2 New Sights into Lineage Commitment
	10.4 Perspective
	References
11: Gene Editing in Hematopoietic Stem Cells
	11.1 Hematopoietic Stem Cells: The Application Frontier of Gene Editing Therapy
	11.2 Gene Editing in HSC
		11.2.1 Development of Gene Editing Tools
		11.2.2 Double-Strand Break (DSB)-Dependent Gene Editing
		11.2.3 DSB-Independent Base Editing and Prime Editing
		11.2.4 In Vivo and In Vitro Gene Editing Element Delivery
	11.3 Advances in Clinical Trials
	11.4 Challenges Toward Clinical Translation of Gene Editing
	11.5 Future Perspectives
	References
12: Aging, Causes, and Rejuvenation of Hematopoietic Stem Cells
	12.1 Introduction
	12.2 Cell Intrinsic Changes in HSCs During Aging
		12.2.1 Inflamm-Aging of HSCs
		12.2.2 Clonal Hematopoiesis in Aging
	12.3 Aging of the Hematopoietic Stem Cell Niche
		12.3.1 Vascular Niche Upon Aging
		12.3.2 Sympathetic Adrenergic Signal Alterations
		12.3.3 Endosteal Niche Degeneration
	12.4 Perspective of Therapeutic Strategies for Anti-HSC Aging
	12.5 Conclusive Remarks
	References