Hematopoietic Stem Cell Biology (eBook)

Stem Cell Biology and Regenerative Medicine 1
Series Editor 1
Preface 1
Acknowledgments 1
Contributors 1
Kondo_Ch01.pdf 12
Principles of Hematopoietic Stem Cell Biology 12
Introduction 12
The Definition and Entity of HSCs 14
Definition of Stem Cells 14
The Functional Heterogeneity of HSCs 15
In vivo and In vitro Assays for HSCs 17
In vivo Assays 17
In vitro Assays 18
The Purification of Mouse HSCs 20
High Degrees of Mouse HSC Purification by Flow Cytometry 20
Toward the Ultimate Purification of HSCs 21
The Fate of HSCs 22
Fate Determination Units 22
Three Types of Cell Division 23
Molecular Basis for Self-Renewal 26
Extrinsic Control of HSCs 26
Intrinsic Control of HSCs 28
Basic Machineries Supporting Self-Renewal 31
Differentiation in HSCs 33
Differentiation Pathways 34
Molecular Control of Differentiation and Lineage Commitment 34
Transcription Factors 35
Epigenetic Changes 35
HSC Homing and Intramedullary Mobilization 37
Perspectives 37
Stem Cell Therapy 37
Cancer Stem Cells and Age-Related Changes in Stem Cells 38
References 40
Kondo_Ch02.pdf 48
Hematopoietic Stem Cells and Their Niche 48
Introduction 48
Stem Cell and Niche 49
Interaction Between Hematopoietic Stem Cell and Niche 50
Osteoblastic Niche 50
ECM Contribution to Osteoblastic Niche 52
Vascular Niche 53
External Oxidative Stress and HSC 55
Seed or Soil? Niche Disruption and Disease 56
Is There a Niche for Cancer Stem Cell? 57
Roles of Niche Against Development, Maintenance, and Proliferation of Cancer 58
Mechanism of Cancer Metastasis Regulated by Niche 60
Novel Cancer Therapy Targeting Cancer Stem Cell and Its Niche 61
Conclusion 64
References 64
Kondo_Ch03.pdf 67
Hematopoietic Stem Cells and Somatic Stem Cells 67
Introduction 68
What Does It Means to Be an Adult Stem Cell? Criteria for Defining Adult Stem Cell Populations 70
Adult Stem Cell Plasticity 71
Hematopoietic Stem Cells: The “Model” of Somatic Stem Cells 72
Embryonic Origins 72
Adult Hematopoietic Stem Cells and Regulation of Hematopoiesis 74
Cell Cycle Regulators in Controlling Hematopoietic Stem Cell Function 75
Extrinsic Regulation of Hematopoietic Stem Cells 77
Other Types of Somatic Stem Cells 78
Non-hematopoietic Stem Cells 79
Drosophila Male Germ Line Stem Cells 79
How the Niche Determines Stem Cell Number 79
How the Niche Determines Stem Cell Identity 81
Interfollicular Epidermis 81
Multipotent Bulge Cells Do Not Normally Contribute to IFE 81
Unipotent Stem Cells in Clinical Therapies 82
Skeletal Muscle Stem Cells 83
Heterogeneity of the Muscle Satellite Cell Compartment 84
Contribution of Other Cell Types to Muscle 84
Stem Cell Markers 85
Origin of Skeletal Muscle Stem Cells 86
Control of Self-Renewal, Proliferation, and Differentiation in Muscle Stem Cell 86
Aging in Stem Cells 87
Tissue Regeneration by Facultative Repair Cells 88
Maintenance in Some Tissues is Primarily Mediated by Non–Stem Cells 88
Concluding Remarks 92
Critical Unanswered Questions in Adult Somatic Stem Cell Biology 92
References 94
Kondo_Ch04.pdf 103
Developmental Biology of Mammalian T-Cell Progenitors: From Early Lymphoid Progenitors to Thymus-Colonizing Cells 103
Introduction 103
Emergence of Lymphoid Differentiation Potential During Early Embryonic Development 106
From Multipotent Stem Cells to Early Lymphoid Precursors 109
Extrathymic Emergence of T-Cell Precursors 112
Dynamics of Human Fetal T-Cell Precursors 115
Mechanisms Regulating Thymus Colonization 116
Conclusion 118
References 119
Kondo_Ch05.pdf 127
GATA1 and GATA2 Function in Hematopoietic Differentiation 127
Introduction 127
The GATA Family of Transcription Factors 128
Expression Profiles of GATA1 and GATA2 129
Transcriptional Regulation of the Gata1 Gene 132
The GATA1 Hematopoietic Regulatory Domain (G1HRD) 132
Sequences and Mechanisms that Regulate Gata1 Transcription 132
Gata1 Hematopoietic Enhancer 133
CACCC Box 134
Double GATA Site 134
Intron SP Element 134
Differences Between Human GATA1 Gene and Mouse Gata1 Gene Transcription 135
Use of G1HRD and Gata1 BACs for Characterization of Erythroid Progenitors 135
Transcription Factors Interacting with GATA1 in Higher Transcriptional Complexes 137
FOG1 (Friend of GATA1) 137
PU.1 137
NLI/Ldb1, LMO2, SCL/TAL1-E2A Complex 139
Domain Function Analyzes of GATA1 140
Posttranslational Modification of GATA1 142
GATA1-Related Leukemias 143
Roles GATA2 Plays in Hematopoietic Stem Cells 144
GATA Switching 144
Perspectives and Closing Remarks 145
Box 1 Transcriptional Control of Hematopoiesis 146
References 146
Kondo_Ch06.pdf 153
Role of the IL-7 Receptor in gd T-Cell Development from Hematopoietic Stem Cells 153
IL-7 and the IL-7R 153
Role of the IL-7R in Early Lymphocyte Development 155
The IL-7R Controls the Recombination in the TCRg Locus 156
STAT5 Controls the Accessibility of Jg Gene Segments 158
STAT5 and the TCRg Locus 162
Control of Vg Recombination by the IL-7R 163
Conclusion 164
References 165
Kondo_Ch07.pdf 170
Dendritic Cell Homeostasis: Physiology and Impact on Disease 170
Introduction 170
Heterogeneity of Dendritic Cells 171
DCs in Nonlymphoid Tissues 171
DCs in Lymphoid Tissues 172
Spleen 173
Lymph Node (LN) 173
Mucosa-Associated Lymphoid Tissues 173
Thymic DCs 173
Plasmacytoid Dendritic Cells in Lymphoid and Nonlymphoid Tissues 174
Turnover of Dendritic Cells 174
Splenic DCs 175
Thymic DCs 175
LN DCs 179
Nonlymphoid Tissue DCs 179
pDCs 180
Human DCs 180
Cytokines in Dendritic Cell Development 181
Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) 181
Flt3L 184
CSF-1 (M-CSF) 185
Transforming Growth Factor-b 186
IL-4, TNFa, LTb, and G-CSF 186
Transcription Factors in Dendritic Cell Development 187
Transcription Factors Affecting “Global” DC Development 188
Ikaros 189
XBP-1 189
Transcription Factors Affecting DC Subtype Diversification 190
RelB 190
PU.1 190
Id2 191
Runx3 191
Differentiation of Dendritic Cell from Hematopoietic Stem and Progenitor Cells 191
Early Hematopoietic DC Development 191
Gradual Downstream Restriction to the DC Lineages 193
Conclusions and Controversies Regarding Groups One and Two DC Progenitor Populations 197
The LC Exception 198
A DC Homeostasis Integrated View 199
Dendritic Cells in Hematologic Disease 201
DC Neoplasms 201
Langerhans Cell Histiocytosis 202
Early pDC Leukemia/Lymphoma (pDCL, CD4+CD56+ Hematodermic Neoplasm) 204
Dendritic Cell Sarcoma 204
DCs in Allogeneic Hematopoietic Cell Transplantation (allo-HCT) 205
Future Directions in Research and Possible Clinical Implementation 207
References 207
Kondo_Ch08.pdf 222
Wnt in Hematopoietic and Leukemic Stem Cells 222
Wnt Pathway 222
Wnt Pathway in Self-Renewal and Differentiation of Hematopoietic Stem Cells 227
Deregulation of the Wnt Pathway in Leukemia Stem Cells 231
Acute Myelogenous Leukemia 231
Acute Lymphoblastic Leukemia 235
Chronic Myeloid Leukemia 238
Chronic Lymphocytic Leukemia 239
Common Themes and Future Directions 241
References 242
Kondo_Backmatter.pdf 253
Stem Cell Biology and Regenerative Medicine 2
Series Editor 2
Preface 5
Acknowledgments 7
Contributors 9