Cell cycle regulation in hematopoietic stem cells

Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in controlling HSC function during both fetal life and in the adult. The cell cycle activity of HSCs is carefully modulated by a complex interplay between cell-intrinsic mechanisms and cell-extrinsic factors produced by the microenvironment. This fine-tuned regulatory network may become altered with age, leading to aberrant HSC cell cycle regulation, degraded HSC function, and hematological malignancy.

[1]  K. Rajewsky,et al.  Tet2 Negatively Regulates Homeostasis and Differentiation of Hematopoietic Stem Cells in Mice , 2011 .

[2]  E. Pietras,et al.  Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies , 2011, Wiley interdisciplinary reviews. Systems biology and medicine.

[3]  Feng-Chun Yang,et al.  Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. , 2011, Blood.

[4]  Akinobu Matsumoto,et al.  p57 is required for quiescence and maintenance of adult hematopoietic stem cells. , 2011, Cell stem cell.

[5]  K. Nakayama,et al.  p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. , 2011, Cell stem cell.

[6]  S. Nimer,et al.  The p53 tumor suppressor protein regulates hematopoietic stem cell fate , 2011, Journal of cellular physiology.

[7]  K. Rajewsky,et al.  Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice , 2011, Proceedings of the National Academy of Sciences.

[8]  O. Abdel-Wahab,et al.  Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. , 2011, Cancer cell.

[9]  P. Opolon,et al.  TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. , 2011, Cancer cell.

[10]  David A. Williams,et al.  Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells , 2011, Proceedings of the National Academy of Sciences.

[11]  P. Guttorp,et al.  The replication rate of human hematopoietic stem cells in vivo. , 2011, Blood.

[12]  S. Rybtsov,et al.  Embryonic origin of the adult hematopoietic system: advances and questions , 2011, Development.

[13]  E. Passegué,et al.  DNA-damage response in tissue-specific and cancer stem cells. , 2011, Cell stem cell.

[14]  Dean Y. Li,et al.  Robo4 cooperates with CXCR4 to specify hematopoietic stem cell localization to bone marrow niches. , 2011, Cell stem cell.

[15]  M. Suematsu,et al.  Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. , 2010, Cell stem cell.

[16]  M. Warr,et al.  Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. , 2010, Cell stem cell.

[17]  W. Maloney,et al.  Stem cells and the aging hematopoietic system. , 2010, Current opinion in immunology.

[18]  Nathan C Boles,et al.  Quiescent hematopoietic stem cells are activated by IFNγ in response to chronic infection , 2010, Nature.

[19]  M. Birnbaum,et al.  AKT1 and AKT2 maintain hematopoietic stem cell function by regulating reactive oxygen species. , 2010, Blood.

[20]  R. Medzhitov,et al.  p53-mediated hematopoietic stem and progenitor cell competition. , 2010, Cell stem cell.

[21]  M. Kharas,et al.  Akt: A double-edged sword for hematopoietic stem cells , 2010, Cell cycle.

[22]  D. Gilliland,et al.  Leukemia stem cells. , 2010, Seminars in cancer biology.

[23]  Yufei Huang,et al.  MicroRNAs control herpesviral dormancy , 2010, Cell Cycle.

[24]  W. Matsui,et al.  Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors. , 2010, Blood.

[25]  I. Weissman,et al.  Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion , 2010, Proceedings of the National Academy of Sciences.

[26]  Nathan C Boles,et al.  Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1. , 2010, Cell stem cell.

[27]  Pernilla Eliasson,et al.  The hematopoietic stem cell niche: Low in oxygen but a nice place to be , 2010, Journal of cellular physiology.

[28]  Yang Liu,et al.  mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells , 2009, Science Signaling.

[29]  I. Weissman,et al.  Niche recycling through division-independent egress of hematopoietic stem cells , 2009, The Journal of experimental medicine.

[30]  E. Laurenti,et al.  Balancing dormant and self-renewing hematopoietic stem cells. , 2009, Current opinion in genetics & development.

[31]  A. Perkins,et al.  Indian hedgehog supports definitive erythropoiesis. , 2009, Blood cells, molecules & diseases.

[32]  G. van Zant,et al.  Effects of aging on hematopoietic stem and progenitor cells. , 2009, Current opinion in immunology.

[33]  Andreas Trumpp,et al.  Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair , 2008, Cell.

[34]  R. Taichman,et al.  Hedgehog signaling is dispensable for adult hematopoietic stem cell function. , 2009, Cell stem cell.

[35]  C. Pronk,et al.  Hematopoietic stem cell ageing is uncoupled from p16INK4A-mediated senescence , 2009, Oncogene.

[36]  J. Sampath,et al.  Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. , 2009, Blood.

[37]  Andreas Trumpp,et al.  IFNα activates dormant haematopoietic stem cells in vivo , 2009, Nature.

[38]  E. Passegué,et al.  JunB protects against myeloid malignancies by limiting hematopoietic stem cell proliferation and differentiation without affecting self-renewal. , 2009, Cancer cell.

[39]  A. Iwama,et al.  TGF-beta as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation. , 2009, Blood.

[40]  Frank J T Staal,et al.  Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation. , 2009, Blood.

[41]  Y. Liu,et al.  p53 regulates hematopoietic stem cell quiescence. , 2009, Cell stem cell.

[42]  D. Bryder,et al.  A Novel Assay to Trace Proliferation History In Vivo Reveals that Enhanced Divisional Kinetics Accompany Loss of Hematopoietic Stem Cell Self-Renewal , 2008, PloS one.

[43]  I. Weissman,et al.  Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family. , 2008, Cell stem cell.

[44]  Jichun Chen,et al.  Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice. , 2008, Experimental hematology.

[45]  Yang Liu,et al.  TSC–mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species , 2008, The Journal of experimental medicine.

[46]  H. Sieburg,et al.  A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. , 2008, Blood.

[47]  E. Passegué,et al.  The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. , 2008, Cell stem cell.

[48]  Yoon-Chi Han,et al.  CXCR4 is required for the quiescence of primitive hematopoietic cells , 2008, The Journal of experimental medicine.

[49]  D. Scadden,et al.  Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. , 2008, Cell stem cell.

[50]  I. Weissman,et al.  Stems Cells and the Pathways to Aging and Cancer , 2008, Cell.

[51]  Lina A. Thoren,et al.  Kit Regulates Maintenance of Quiescent Hematopoietic Stem Cells1 , 2008, The Journal of Immunology.

[52]  D. Scadden,et al.  Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation , 2008, Nature Reviews Genetics.

[53]  Lina A. Thoren,et al.  Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. , 2007, Cell stem cell.

[54]  T. Reya,et al.  Loss of β-Catenin Impairs the Renewal of Normal and CML Stem Cells In Vivo , 2007 .

[55]  Ulrich H. von Andrian,et al.  Immunosurveillance by Hematopoietic Progenitor Cells Trafficking through Blood, Lymph, and Peripheral Tissues , 2007, Cell.

[56]  Shenghui He,et al.  Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU , 2007, Nature.

[57]  Ronald A. DePinho,et al.  How stem cells age and why this makes us grow old , 2007, Nature Reviews Molecular Cell Biology.

[58]  S. Morrison,et al.  Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells , 2007, Cell.

[59]  Chad A Shaw,et al.  Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation , 2007, PLoS biology.

[60]  S. Orkin,et al.  Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment , 2007, Cell.

[61]  Anastasia Nijnik,et al.  DNA repair is limiting for haematopoietic stem cells during ageing , 2007, Nature.

[62]  Irving L. Weissman,et al.  Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age , 2007, Nature.

[63]  A. Iwama,et al.  Cytokine Signaling, Lipid Raft Clustering, and HSC Hibernation , 2007, Annals of the New York Academy of Sciences.

[64]  E. Laurenti,et al.  Dormant and Self‐Renewing Hematopoietic Stem Cells and Their Niches , 2007, Annals of the New York Academy of Sciences.

[65]  S. Nishikawa,et al.  Cell tracing shows the contribution of the yolk sac to adult haematopoiesis , 2007, Nature.

[66]  D. Kent,et al.  Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties , 2007, Proceedings of the National Academy of Sciences.

[67]  L. Bystrykh,et al.  A Limited Role for p21Cip1/Waf1 in Maintaining Normal Hematopoietic Stem Cell Functioning , 2007, Stem cells.

[68]  C. Deng,et al.  Smad4 is critical for self-renewal of hematopoietic stem cells , 2007, The Journal of experimental medicine.

[69]  L. Donehower,et al.  The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. , 2007, Blood.

[70]  S. Armstrong,et al.  FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress , 2007, Cell.

[71]  H. Nakauchi,et al.  Adult mouse hematopoietic stem cells: purification and single-cell assays , 2006, Nature Protocols.

[72]  David G Kent,et al.  Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect. , 2006, The Journal of clinical investigation.

[73]  R. DePinho,et al.  Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a , 2006, Nature.

[74]  A. Iwama,et al.  Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice , 2006, The Journal of experimental medicine.

[75]  A. Iwama,et al.  Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells , 2006, The EMBO journal.

[76]  D. Bryder,et al.  Prolonged Cell Cycle Transit Is a Defining and Developmentally Conserved Hemopoietic Stem Cell Property1 , 2006, The Journal of Immunology.

[77]  S. Orkin,et al.  Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[78]  S. Morrison,et al.  Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells , 2006, Nature.

[79]  Xi C. He,et al.  PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention , 2006, Nature.

[80]  Keisuke Ito,et al.  Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells , 2006, Nature Medicine.

[81]  S. Heimfeld,et al.  HES1 Inhibits Cycling of Hematopoietic Progenitor Cells via DNA Binding , 2006, Stem cells.

[82]  E. Brown,et al.  Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor , 2006, Nature.

[83]  A. Trumpp,et al.  Bone-marrow haematopoietic-stem-cell niches , 2006, Nature Reviews Immunology.

[84]  Irving L. Weissman,et al.  Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates , 2005, The Journal of experimental medicine.

[85]  J. Aster,et al.  Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. , 2005, Cell stem cell.

[86]  David A. Williams,et al.  Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization , 2005, Nature Medicine.

[87]  I. Weissman,et al.  Cell intrinsic alterations underlie hematopoietic stem cell aging. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[88]  Jiri Bartek,et al.  Cell-cycle checkpoints and cancer , 2004, Nature.

[89]  J. Massagué,et al.  G1 cell-cycle control and cancer , 2004, Nature.

[90]  S. Orkin,et al.  The placenta is a niche for hematopoietic stem cells. , 2004, Developmental cell.

[91]  K. Akashi,et al.  Mouse Development and Cell Proliferation in the Absence of D-Cyclins , 2004, Cell.

[92]  Pierre Dubus,et al.  Mammalian Cells Cycle without the D-Type Cyclin-Dependent Kinases Cdk4 and Cdk6 , 2004, Cell.

[93]  Keisuke Ito,et al.  Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche , 2004, Cell.

[94]  D. Scadden,et al.  In vivo self-renewing divisions of haematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C , 2004, Nature Cell Biology.

[95]  I. Weissman,et al.  Circulation and Chemotaxis of Fetal Hematopoietic Stem Cells , 2004, PLoS biology.

[96]  L. Scott,et al.  Deletion of α4 Integrins from Adult Hematopoietic Cells Reveals Roles in Homeostasis, Regeneration, and Homing , 2003, Molecular and Cellular Biology.

[97]  M. Goumans,et al.  TGF-beta signaling-deficient hematopoietic stem cells have normal self-renewal and regenerative ability in vivo despite increased proliferative capacity in vitro. , 2003, Blood.

[98]  A. Bernstein,et al.  Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[99]  Jichun Chen,et al.  Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. , 2003, Experimental hematology.

[100]  G. Sauvageau,et al.  Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells , 2003, Nature.

[101]  Irving L. Weissman,et al.  Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells , 2003, Nature.

[102]  R. Alon,et al.  TGF‐β1 enhances SDF‐1α‐induced chemotaxis and homing of naive T cells by up‐regulating CXCR4 expression and downstream cytoskeletal effector molecules , 2002, European journal of immunology.

[103]  Charles J. Sherr,et al.  The INK4a/ARF network in tumour suppression , 2001, Nature Reviews Molecular Cell Biology.

[104]  D. Scadden,et al.  Stem cell repopulation efficiency but not pool size is governed by p27kip1 , 2000, Nature Medicine.

[105]  D. Scadden,et al.  Hematopoietic stem cell quiescence maintained by p21cip1/waf1. , 2000, Science.

[106]  J. Palis,et al.  Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. , 1999, Development.

[107]  I. Weissman,et al.  In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[108]  M. Rudnicki,et al.  Strain-Dependent Myeloid Hyperplasia, Growth Deficiency, and Accelerated Cell Cycle in Mice Lacking the Rb-Related p107 Gene , 1998, Molecular and Cellular Biology.

[109]  R. Bronson,et al.  Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[110]  Y. Furukawa,et al.  Cell cycle regulation of hematopoietic stem cells. , 1998, Human cell.

[111]  S. Elledge,et al.  Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith–Wiedemann syndrome , 1997, Nature.

[112]  M. Barbacid,et al.  Ablation of the CDK inhibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development. , 1997, Genes & development.

[113]  A. Medvinsky,et al.  Definitive Hematopoiesis Is Autonomously Initiated by the AGM Region , 1996, Cell.

[114]  S. Nishikawa,et al.  Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 , 1996, Nature.

[115]  R. Weinberg,et al.  Shared role of the pRB-related p130 and p107 proteins in limb development. , 1996, Genes & development.

[116]  G. Stamp,et al.  Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. , 1995, Genes & development.

[117]  A. Kulkarni,et al.  Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. , 1995, Development.

[118]  P. Ingham,et al.  Hedgehog signaling. , 2012, Cold Spring Harbor perspectives in biology.

[119]  Tannishtha Reya,et al.  Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia , 2009, Nature.

[120]  Rudolf Jaenisch,et al.  Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells , 2009, Nature Biotechnology.

[121]  E. Forsberg,et al.  Parsing the niche code: the molecular mechanisms governing hematopoietic stem cell adhesion and differentiation. , 2009, Haematologica.

[122]  H. Macdonald,et al.  Simultaneous loss of beta- and gamma-catenin does not perturb hematopoiesis or lymphopoiesis. , 2008, Blood.

[123]  H. Macdonald,et al.  Simultaneous loss of β- and γ-catenin does not perturb hematopoiesis or lymphopoiesis , 2008 .

[124]  T. Reya,et al.  Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. , 2007, Cancer cell.

[125]  宮本 佳奈.  Foxo3a is essential for maintenance of the hematopoietic stem cell pool , 2007 .

[126]  D O Morgan,et al.  Cyclin-dependent kinases: engines, clocks, and microprocessors. , 1997, Annual review of cell and developmental biology.

[127]  R. Schofield.  The relationship between the spleen colony-forming cell and the haemopoietic stem cell. , 1978, Blood cells.

[128]  J. Massagué,et al.  Transforming growth factor (cid:1) -induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation , 2022 .

[129]  L. Zon,et al.  Hematopoiesis: An Evolving Paradigm for Stem Cell Biology , 2008, Cell.

[130]  D. Scadden,et al.  Hematopoietic Stem Cell Quiescence Maintained by p 21 cip 1 / waf 1 , 2022 .