Skip to main content
SpringerLink
Log in

Notch Signaling and Development of the Hematopoietic System

  • Chapter
Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 727))

Abstract

Notch signaling exerts multiple important functions in the hematopoietic system. Notch1-mediated signals are essential to induce the onset of definitive hematopoiesis within specialized domains of hemogenic endothelium in the fetal dorsal aorta. In contrast, Notch is dispensable for the subsequent maintenance of hematopoietic stem cells in the adult bone marrow. Notch is a key regulator of early T-cell development in the thymus. An expanding number of hematopoietic and lymphoid cell types have been reported to receive context-dependent inputs from the Notch pathway that regulate their differentiation and function. Progress in the field will continue to bring fundamental information about hematopoiesis and practical insights into the potential to modulate Notch signaling for therapeutic purposes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ellisen LW, Bird J, West DC et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 1991; 66(4):649–661.

    PubMed  CAS  Google Scholar 

  2. Pear WS, Aster JC, Scott ML et al. Exclusive development of T-cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J. Exp. Med 1996; 183(5):2283–2291.

    PubMed  CAS  Google Scholar 

  3. Bray SJ. Notch signalling: A simple pathway becomes complex. Nat Rev Mol Cell Biol 2006; 7(9):678–689.

    PubMed  CAS  Google Scholar 

  4. Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 2009; 137(2):216–233.

    PubMed  CAS  Google Scholar 

  5. Maillard I, Fang T, Pear WS. Regulation of lymphoid development, differentiation and function by the Notch pathway. Annu Rev Immunol 2005; 23:945–974.

    PubMed  CAS  Google Scholar 

  6. Tanigaki K, Honjo T. Regulation of lymphocyte development by Notch signaling. Nat Immunol 2007; 8(5):451–456.

    PubMed  CAS  Google Scholar 

  7. Aster JC, Pear WS, Blacklow SC. Notch signaling in leukemia. Annu Rev Pathol 2008; 3:587–613.

    PubMed  CAS  Google Scholar 

  8. Ferrando AA. The role of NOTCH1 signaling in T-ALL. Hematology Am Soc Hematol Educ Program. 2009:353–361.

    Google Scholar 

  9. Yuan JS, Kousis PC, Suliman S et al. Functions of notch signaling in the immune system: consensus and controversies. Annu Rev Immunol 2010; 28:343–365.

    PubMed  Google Scholar 

  10. Radtke F, Fasnacht N, Macdonald HR. Notch Signaling in the Immune System. Immunity 2010; 32(1):14–27.

    PubMed  CAS  Google Scholar 

  11. Ladi E, Nichols JT, Ge W et al. The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. J Cell Biol 2005; 170(6):983–992.

    PubMed  CAS  Google Scholar 

  12. Radtke F, Wilson A, Stark G et al. Deficient T-cell fate specification in mice with an induced inactivation of Notch1. Immunity 1999; 10(5):547–558.

    PubMed  CAS  Google Scholar 

  13. Koch U, Fiorini E, Benedito R et al. Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T-cell lineage commitment. J Exp Med 2008; 205(11):2515–2523.

    PubMed  CAS  Google Scholar 

  14. Saito T, Chiba S, Ichikawa M et al. Notch2 is preferentially expressed in mature B-cells and indispensable for marginal zone B lineage development. Immunity 2003; 18(5):675–685.

    PubMed  CAS  Google Scholar 

  15. Hozumi K, Negishi N, Suzuki D et al. Delta-like 1 is necessary for the generation of marginal zone B-cells but not T-cells in vivo. Nat Immunol 2004; 5(6):638–644.

    PubMed  CAS  Google Scholar 

  16. Yang LT, Nichols JT, Yao C et al. Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1. Mol Biol Cell 2005; 16(2):927–942.

    PubMed  CAS  Google Scholar 

  17. Besseyrias V, Fiorini E, Strobl LJ et al. Hierarchy of Notch-Delta interactions promoting T-cell lineage commitment and maturation. J Exp Med 2007; 204(2):331–343.

    PubMed  Google Scholar 

  18. Bruckner K, Perez L, Clausen H et al. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 2000; 406(6794):411–415.

    PubMed  CAS  Google Scholar 

  19. Haltiwanger RS, Stanley P. Modulation of receptor signaling by glycosylation: fringe is an O-fucose-beta1, 3-N-acetylglucosaminyltransferase. Biochim Biophys Acta 2002; 1573(3):328–335.

    PubMed  CAS  Google Scholar 

  20. Benedito R, Roca C, Sorensen I et al. The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 2009; 137(6):1124–1135.

    PubMed  CAS  Google Scholar 

  21. Visan I, Yuan JS, Tan JB et al. Regulation of intrathymic T-cell development by Lunatic Fringe-Notch1 interactions. Immunol Rev 2006; 209:76–94.

    PubMed  CAS  Google Scholar 

  22. Logeat F, Bessia C, Brou C et al. The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci USA 1998; 95(14):8108–8112.

    PubMed  CAS  Google Scholar 

  23. De Strooper B, Annaert W. Novel Research Horizons for Presenilins and gamma-Secretases in Cell Biology and Disease. Annu Rev Cell Dev Biol 2010 epub ahead of print.

    Google Scholar 

  24. Mumm JS, Schroeter EH, Saxena MT et al. A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Molecular Cell 2000; 5:197–206.

    PubMed  CAS  Google Scholar 

  25. Brou C, Logeat F, Gupta N et al. A novel proteolytic cleavage involved in Notch signaling: The role of the disintegrin-metalloprotease TACE. Mol. Cell 2000; 5:207–216.

    PubMed  CAS  Google Scholar 

  26. Tian L, Wu X, Chi C et al. ADAM10 is essential for proteolytic activation of Notch during thymocyte development. Int Immunol 2008; 20(9):1181–1187.

    PubMed  CAS  Google Scholar 

  27. Gibb DR, El Shikh M, Kang DJ et al. ADAM10 is essential for Notch2-dependent marginal zone B-cell development and CD23 cleavage in vivo. J Exp Med 2010; 207(3):623–635.

    PubMed  CAS  Google Scholar 

  28. Gordon WR, Roy M, Vardar-Ulu D et al. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood 2009; 113(18):4381–4390.

    PubMed  CAS  Google Scholar 

  29. Gordon WR, Vardar-Ulu D, Histen G et al. Structural basis for autoinhibition of Notch. Nat Struct Mol Biol 2007; 14(4):295–300.

    PubMed  CAS  Google Scholar 

  30. Weng AP, Ferrando AA, Lee W et al. Activating mutations of NOTCH1 in human T-cell acute lymphoblastic leukemia. Science 2004; 306(5694):269–271.

    PubMed  CAS  Google Scholar 

  31. Li K, Li Y, Wu W et al. Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J Biol Chem 2008; 283(12):8046–8054.

    PubMed  CAS  Google Scholar 

  32. Wu Y, Cain-Hom C, Choy L et al. Therapeutic antibody targeting of individual Notch receptors. Nature 2010; 464(7291):1052–1057.

    PubMed  CAS  Google Scholar 

  33. De Strooper B, Annaert W, Cupers P et al. A presenilin-1-dependent-secretase-like protease mediates release of Notch intracellular domain. Nature 1999; 398:518–522.

    PubMed  Google Scholar 

  34. Stempfle D, Kanwar R, Loewer A et al. In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity. Mol Cell Biol 2010; 30(13):3165–3175.

    PubMed  CAS  Google Scholar 

  35. Selkoe D, Kopan R. Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration. Annu Rev Neurosci 2003; 26:565–597.

    PubMed  CAS  Google Scholar 

  36. Wolfe MS, Haass C. The Role of presenilins in gamma-secretase activity. J Biol Chem 2001; 276(8):5413–5416.

    PubMed  CAS  Google Scholar 

  37. Wolfe MS. gamma-Secretase inhibitors as molecular probes of presenilin function. J Mol Neurosci 2001; 17(2):199–204.

    PubMed  CAS  Google Scholar 

  38. Jarriault S, Brou C, Logeat F et al. Signalling downstream of activated mammalian Notch. Nature 1995; 377(6547):355–358.

    PubMed  CAS  Google Scholar 

  39. Tamura K, Taniguchi Y, Minoguchi S et al. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H). Current Biology 1995; 5(12):1416–1423.

    PubMed  CAS  Google Scholar 

  40. Jeffries S, Robbins DJ, Capobianco AJ. Characterization of a High-Molecular-Weight Notch Complex in the Nucleus of Notch(ic)-Transformed RKE Cells and in a Human T-Cell Leukemia Cell Line. Mol Cell Biol 2002; 22(11):3927–3941.

    PubMed  CAS  Google Scholar 

  41. Nam Y, Sliz P, Song L et al. Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell 2006; 124(5):973–983.

    PubMed  CAS  Google Scholar 

  42. Kuroda K, Han H, Tani S et al. Regulation of marginal zone B-cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity 2003; 18(2):301–312.

    PubMed  CAS  Google Scholar 

  43. Oswald F, Kostezka U, Astrahantseff K et al. SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J 2002; 21(20):5417–5426.

    PubMed  CAS  Google Scholar 

  44. Liefke R, Oswald F, Alvarado C et al. Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex. Genes Dev 2010; 24(6):590–601.

    PubMed  CAS  Google Scholar 

  45. Petcherski AG, Kimble J. Mastermind is a putative activator for Notch. Curr Biol 2000; 10(13):R471–473.

    PubMed  CAS  Google Scholar 

  46. Wu L, Aster JC, Blacklow SC et al. MAML1, a human homologue of drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet 2000; 26(4):484–489.

    PubMed  CAS  Google Scholar 

  47. Wu L, Sun T, Kobayashi K et al. Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors. Mol Cell Biol 2002; 22(21):7688–7700.

    PubMed  CAS  Google Scholar 

  48. Maillard I, Weng AP, Carpenter AC et al. Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood 2004; 104(6):1696–1702.

    PubMed  CAS  Google Scholar 

  49. Weng AP, Nam Y, Wolfe MS et al. Growth suppression of preT acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol 2003; 23(2):655–664.

    PubMed  CAS  Google Scholar 

  50. Moellering RE, Cornejo M, Davis TN et al. Direct inhibition of the NOTCH transcription factor complex. Nature 2009; 462(7270):182–188.

    PubMed  CAS  Google Scholar 

  51. Ikawa T, Kawamoto H, Goldrath AW et al. E proteins and Notch signaling cooperate to promote T-cell lineage specification and commitment. J Exp Med 2006; 203(5):1329–1342.

    PubMed  CAS  Google Scholar 

  52. Wall DS, Mears AJ, McNeill B et al. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J Cell Biol 2009; 184(1):101–112.

    PubMed  CAS  Google Scholar 

  53. Ingram WJ, McCue KI, Tran TH et al. Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene 2008; 27(10):1489–1500.

    PubMed  CAS  Google Scholar 

  54. Maekawa Y, Minato Y, Ishifune C et al. Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T-cell cytotoxicity. Nat Immunol 2008; 9(10):1140–1147.

    PubMed  CAS  Google Scholar 

  55. Samon JB, Champhekar A, Minter LM et al. Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T-cells. Blood 2008; 1126(5):1813–1821.

    Google Scholar 

  56. Hadland BK, Huppert SS, Kanungo J et al. A requirement for Notch1 distinguishes two phases of definitive hematopoiesis during development. Blood 2004; 104(10):3097–3105.

    PubMed  CAS  Google Scholar 

  57. Kumano K, Chiba S, Kunisato A et al. Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells. Immunity 2003; 18(5):699–711.

    PubMed  CAS  Google Scholar 

  58. Bertrand JY, Cisson JL, Stachura DL et al. Notch signaling distinguishes 2 waves of definitive hematopoiesis in the zebrafish embryo. Blood 2010; 115(14):2777–2783.

    PubMed  CAS  Google Scholar 

  59. Tanigaki K, Han H, Yamamoto N et al. Notch-RBP-J signaling is involved in cell fate determination of marginal zone B-cells. Nat Immunol 2002; 3(5):443–450.

    PubMed  CAS  Google Scholar 

  60. Tan JB, Visan I, Yuan JS, Guidos CJ. Requirement for Notch1 signals at sequential early stages of intrathymic T-cell development. Nat Immunol 2005; 6(7):671–679.

    PubMed  CAS  Google Scholar 

  61. Sambandam A, Maillard I, Zediak VP et al. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat Immunol 2005; 6(7):663–670.

    PubMed  CAS  Google Scholar 

  62. Mercher T, Cornejo MG, Sears C et al. Notch signaling specifies megakaryocyte development from hematopoietic stem cells. Cell Stem Cell 2008; 3(3):314–326.

    PubMed  CAS  Google Scholar 

  63. Caton ML, Smith-Raska MR, Reizis B. Notch-RBP-J signaling controls the homeostasis of CD8-dendritic cells in the spleen. J Exp Med 2007; 204(7):1653–1664.

    PubMed  CAS  Google Scholar 

  64. Thomas M, Calamito M, Srivastava B, Maillard I, Pear WS, Allman D. Notch activity synergizes with B-cell-receptor and CD40 signaling to enhance B-cell activation. Blood 2007; 109(8):3342–3350.

    PubMed  CAS  Google Scholar 

  65. Osborne BA, Minter LM. Notch signalling during peripheral T-cell activation and differentiation. Nat Rev Immunol 2007; 7(1):64–75.

    PubMed  CAS  Google Scholar 

  66. Amsen D, Antov A, Flavell RA. The different faces of Notch in T-helper-cell differentiation. Nat Rev Immunol 2009; 9(2):116–124.

    PubMed  CAS  Google Scholar 

  67. Gao J, Graves S, Koch U et al. Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell 2009; 4(6):548–558.

    PubMed  CAS  Google Scholar 

  68. Maillard I, Koch U, Dumortier A et al. Canonical Notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell 2008; 2(4):356–366.

    PubMed  CAS  Google Scholar 

  69. Mancini SJ, Mantei N, Dumortier A et al. Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation. Blood 2005; 105(6):2340-2342.

    Google Scholar 

  70. Jaffredo T, Gautier R, Brajeul V et al. Tracing the progeny of the aortic hemangioblast in the avian embryo. Dev Biol 2000; 224(2):204–214.

    PubMed  CAS  Google Scholar 

  71. Dzierzak E, Speck NA. Of lineage and legacy: the development of mammalian hematopoietic stem cells. Nat Immunol 2008; 9(2):129–136.

    PubMed  CAS  Google Scholar 

  72. Gekas C, Dieterlen-Lievre F, Orkin SH et al. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005; 8(3):365–375.

    PubMed  CAS  Google Scholar 

  73. Boisset JC, van Cappellen W, Andrieu-Soler C et al. In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium. Nature 2010; 464(7285):116–120.

    PubMed  CAS  Google Scholar 

  74. Bertrand JY, Chi NC, Santoso B et al. Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 2010; 464(7285):108–111.

    PubMed  CAS  Google Scholar 

  75. Kissa K, Herbomel P. Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature 2010; 464(7285):112–115.

    PubMed  CAS  Google Scholar 

  76. North T, Gu TL, Stacy T et al. Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development 1999; 126(11):2563–2575.

    PubMed  CAS  Google Scholar 

  77. Burns CE, Traver D, Mayhall E et al. Hematopoietic stem cell fate is established by the Notch-Runx pathway. Genes Dev 2005; 19(19):2331–2342.

    PubMed  CAS  Google Scholar 

  78. Chen MJ, Yokomizo T, Zeigler BM et al. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 2009; 457(7231):887–891.

    PubMed  CAS  Google Scholar 

  79. Nakagawa M, Ichikawa M, Kumano K et al. AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis. Blood 2006; 108(10):3329–3334.

    PubMed  CAS  Google Scholar 

  80. Robert-Moreno A, Espinosa L, de la Pompa JL et al. RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development 2005; 132(5):1117–1126.

    PubMed  CAS  Google Scholar 

  81. Nottingham WT, Jarratt A, Burgess M et al. Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer. Blood 2007; 110(13):4188–4197.

    PubMed  CAS  Google Scholar 

  82. Krebs LT, Xue Y, Norton CR et al. Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 2000; 14(11):1343–1352.

    PubMed  CAS  Google Scholar 

  83. Limbourg FP, Takeshita K, Radtke F et al. Essential role of endothelial Notch1 in angiogenesis. Circulation 2005; 111(14):1826–1832.

    PubMed  CAS  Google Scholar 

  84. Noguera-Troise I, Daly C, Papadopoulos NJ et al. Blockade of Dll4 inhibits tumour growth by promoting nonproductive angiogenesis. Nature 2006; 444(7122):1032–1037.

    PubMed  CAS  Google Scholar 

  85. Hellstrom M, Phng LK, Hofmann JJ et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 2007; 445(7129):776–780.

    PubMed  Google Scholar 

  86. Kim YH, Hu H, Guevara-Gallardo S et al. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development 2008; 135(22):3755–3764.

    PubMed  CAS  Google Scholar 

  87. Lawson ND, Scheer N, Pham VN et al. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development 2001; 128(19):3675–3683.

    PubMed  CAS  Google Scholar 

  88. Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998; 93(5):741–753.

    PubMed  CAS  Google Scholar 

  89. You LR, Lin FJ, Lee CT et al. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature 2005; 435(7038):98–104.

    PubMed  CAS  Google Scholar 

  90. Robert-Moreno A, Guiu J, Ruiz-Herguido C et al. Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1. EMBO J 2008; 27(13):1886–1895.

    PubMed  CAS  Google Scholar 

  91. Yoon MJ, Koo BK, Song R et al. Mind bomb-1 is essential for intraembryonic hematopoiesis in the aortic endothelium and the subaortic patches. Mol Cell Biol 2008; 28(15):4794–4804.

    PubMed  CAS  Google Scholar 

  92. Itoh M, Kim CH, Palardy G et al. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 2003; 4(1):67–82.

    PubMed  CAS  Google Scholar 

  93. Gale NW, Dominguez MG, Noguera I et al. Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc Natl Acad Sci USA 2004; 101(45):15949–15954.

    PubMed  CAS  Google Scholar 

  94. North TE, Goessling W, Peeters M et al. Hematopoietic stem cell development is dependent on blood flow. Cell 2009; 137(4):736–748.

    PubMed  CAS  Google Scholar 

  95. North TE, Goessling W, Walkley CR et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 2007; 447(7147):1007–1011.

    PubMed  CAS  Google Scholar 

  96. Goessling W, North TE, Loewer S et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009; 136(6):1136–1147.

    PubMed  CAS  Google Scholar 

  97. Wilkinson RN, Pouget C, Gering M et al. Hedgehog and Bmp polarize hematopoietic stem cell emergence in the zebrafish dorsal aorta. Dev Cell 2009; 16(6):909–916.

    PubMed  CAS  Google Scholar 

  98. Guo M, Jan LY, Jan YN. Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Neuron 1996; 17(1):27–41.

    PubMed  Google Scholar 

  99. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999; 284(5415):770–776.

    PubMed  CAS  Google Scholar 

  100. Spana EP, Doe CQ. Numb antagonizes Notch signaling to specify sibling neuron cell fates. Neuron 1996; 17(1):21–26.

    PubMed  CAS  Google Scholar 

  101. Milner LA, Kopan R, Martin DI et al. A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+hematopoietic precursors. Blood 1994; 83(8):2057–2062.

    PubMed  CAS  Google Scholar 

  102. Li L, Milner LA, Deng Y et al. The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity 1998; 8(1):43–55.

    PubMed  CAS  Google Scholar 

  103. Varnum-Finney B, Purton LE, Yu M et al. The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells. Blood 1998; 91(11):4084–4091.

    PubMed  CAS  Google Scholar 

  104. Walker L, Carlson A, Tan-Pertel HT et al. The notch receptor and its ligands are selectively expressed during hematopoietic development in the mouse. Stem Cells 2001; 19(6):543–552.

    PubMed  CAS  Google Scholar 

  105. Walker L, Lynch M, Silverman S et al. The Notch/Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro. Stem Cells 1999; 17(3):162–171.

    PubMed  CAS  Google Scholar 

  106. Delaney C, Varnum-Finney B, Aoyama K, Brashem-Stein C, Bernstein ID. Dose-dependent effects of the Notch ligand Delta1 on ex vivo differentiation and in vivo marrow repopulating ability of cord blood cells. Blood 2005; 106(8):2693–2699.

    PubMed  CAS  Google Scholar 

  107. Ohishi K, Varnum-Finney B, Bernstein ID. Delta-1 enhances marrow and thymus repopulating ability of human CD34 (+)CD38 (−) cord blood cells. J Clin Invest 2002; 110(8):1165–1174.

    PubMed  CAS  Google Scholar 

  108. Varnum-Finney B, Brashem-Stein C, Bernstein ID. Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability. Blood 2003; 101(5):1784–1789.

    PubMed  CAS  Google Scholar 

  109. Varnum-Finney B, Xu L, Brashem-Stein C et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive notch1 signaling. Nat Med 2000; 6(11):1278–1281.

    PubMed  CAS  Google Scholar 

  110. Calvi LM, Adams GB, Weibrecht KW et al. Osteoblastic cells regulate the hematopoietic stem cell niche. Nature 2003; 425(6960):841–846.

    PubMed  CAS  Google Scholar 

  111. Stier S, Cheng T, Dombkowski D et al. Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome. Blood 2002; 99(7):2369–2378.

    PubMed  CAS  Google Scholar 

  112. Kunisato A, Chiba S, Nakagami-Yamaguchi E et al. HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo. Blood 2003; 101(5):1777–1783.

    PubMed  CAS  Google Scholar 

  113. Butler JM, Nolan DJ, Vertes EL et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 2010; 6(3):251–264.

    PubMed  CAS  Google Scholar 

  114. Delaney C, Heimfeld S, Brashem-Stein C et al. Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010; 16(2):232–236.

    PubMed  CAS  Google Scholar 

  115. Duncan AW, Rattis FM, DiMascio LN et al. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005; 6(3):314–322.

    PubMed  CAS  Google Scholar 

  116. Maeda T, Merghoub T, Hobbs RM et al. Regulation of B versus T-lymphoid lineage fate decision by the proto-oncogene LRF. Science 2007; 316(5826):860–866.

    PubMed  CAS  Google Scholar 

  117. Pui JC, Allman D, Xu L et al. Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 1999; 11(3):299–308.

    PubMed  CAS  Google Scholar 

  118. Dong Y, Jesse AM, Kohn A et al. RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development. Development 2010; 137(9):1461–1471.

    PubMed  CAS  Google Scholar 

  119. Hilton MJ, Tu X, Wu X et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 2008; 14(3):306–314.

    PubMed  CAS  Google Scholar 

  120. Visan I, Tan JB, Yuan JS et al. Regulation of T-lymphopoiesis by Notch1 and Lunatic fringe-mediated competition for intrathymic niches. Nat Immunol 2006; 7(6):634–643.

    PubMed  CAS  Google Scholar 

  121. Schmitt TM, Zuniga-Pflucker JC. Induction of T-cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 2002; 17(6):749–756.

    PubMed  CAS  Google Scholar 

  122. Mohtashami M, Shah DK, Nakase H et al. Direct comparison of Dll1-and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes. J Immunol 2010; 185(2):867–876.

    PubMed  CAS  Google Scholar 

  123. Hadland BK, Manley NR, Su D et al. Gamma-secretase inhibitors repress thymocyte development. Proc Natl Acad Sci USA 2001; 98(13):7487–7491.

    PubMed  CAS  Google Scholar 

  124. Doerfler P, Shearman MS, Perlmutter RM. Presenilin-dependent gamma-secretase activity modulates thymocyte development. Proc Natl Acad Sci USA 2001; 98(16):9312–9317.

    PubMed  CAS  Google Scholar 

  125. Han H, Tanigaki K, Yamamoto N et al. Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. Int Immunol 2002; 14(6):637–645.

    PubMed  CAS  Google Scholar 

  126. Maillard I, Schwarz BA, Sambandam A et al. Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation. Blood 2006; 107(9):3511–3519.

    PubMed  CAS  Google Scholar 

  127. Harman BC, Jenkinson WE, Parnell SM et al. T/B lineage choice occurs prior to intrathymic notch signalling. Blood 2005; 106(3): 886–892.

    PubMed  CAS  Google Scholar 

  128. Taghon T, Yui MA, Pant R et al. Developmental and molecular characterization of emerging beta-and gammadelta-selected preT-cells in the adult mouse thymus. Immunity 2006; 24(1):53–64.

    PubMed  CAS  Google Scholar 

  129. Yui MA, Feng N, Rothenberg EV. Fine-scale staging of T-cell lineage commitment in adult mouse thymus. J Immunol 2010; 185(1):284–293.

    PubMed  CAS  Google Scholar 

  130. Wilson A, MacDonald HR, Radtke F. Notch 1-deficient common lymphoid precursors adopt a B-cell fate in the thymus. J Exp Med 2001; 194(7):1003–1012.

    PubMed  CAS  Google Scholar 

  131. Bell JJ, Bhandoola A. The earliest thymic progenitors for T-cells possess myeloid lineage potential. Nature 2008; 452(7188):764–767.

    PubMed  CAS  Google Scholar 

  132. Feyerabend TB, Terszowski G, Tietz A et al. Deletion of Notch1 converts pro T-cells to dendritic cells and promotes thymic B-cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity 2009; 30(1):67–79.

    PubMed  CAS  Google Scholar 

  133. Ciofani M, Knowles GC, Wiest DL et al. Stage-Specific and Differential Notch Dependency at the alphabeta and gammadelta T Lineage Bifurcation. Immunity 2006; 25(1):105–116.

    PubMed  CAS  Google Scholar 

  134. Garbe AI, Krueger A, Gounari F et al. Differential synergy of Notch and T-cell receptor signaling determines alphabeta versus gammadelta lineage fate. J Exp Med 2006; 203(6):1579–1590.

    PubMed  CAS  Google Scholar 

  135. Van de Walle I, De Smet G, De Smedt M et al. An early decrease in Notch activation is required for human TCR-alphabeta lineage differentiation at the expense of TCR-gammadelta T-cells. Blood 2009; 113(13):2988–2998.

    PubMed  Google Scholar 

  136. Ciofani M, Zuniga-Pflucker JC. Notch promotes survival of preT-cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 2005; 6(9):881–888.

    PubMed  CAS  Google Scholar 

  137. Weng AP, Millholland JM, Yashiro-Ohtani Y et al c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006; 20(15):2096–2109.

    PubMed  CAS  Google Scholar 

  138. Gonzalez-Garcia S, Garcia-Peydro M, Martin-Gayo E et al. CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia. J Exp Med 2009; 206(4):779–791.

    PubMed  CAS  Google Scholar 

  139. Yashiro-Ohtani Y, He Y, Ohtani T et al. Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A. Genes and Development 2009; 23(14):1665–1676.

    PubMed  CAS  Google Scholar 

  140. Wolfer A, Bakker T, Wilson A et al. Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development. Nat Immunol 2001; 2(3):235–241.

    PubMed  CAS  Google Scholar 

  141. Tanigaki K, Tsuji M, Yamamoto N et al. Regulation of alphabeta/gammadelta T-cell lineage commitment and peripheral T-cell responses by Notch/RBP-J signaling. Immunity 2004; 20(5):611–622.

    PubMed  CAS  Google Scholar 

  142. Deftos ML, Huang E, Ojala EW et al. Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes. Immunity 2000; 13(1):73–84.

    PubMed  CAS  Google Scholar 

  143. Fowlkes BJ, Robey EA. A reassessment of the effect of activated Notch1 on CD4 and CD8 T-cell development. J Immunol 2002; 169(4):1817–1821.

    PubMed  CAS  Google Scholar 

  144. Sandy AR, Maillard I. Notch signaling in the hematopoietic system. Expert Opin Biol Ther 2009; 9(11):1383–1398.

    PubMed  Google Scholar 

  145. Wu L, Maillard I, Nakamura M et al. The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development. Blood 2007; 110(10):3618–3623.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA

    Ashley R. Sandy, Morgan Jones & Ivan Maillard

  2. Graduate Program of Immunology, University of Michigan, Ann Arbor, Michigan, USA

    Ashley R. Sandy

  3. Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA

    Morgan Jones

  4. Division of Hematology-Onocology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Ivan Maillard

  5. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA

    Ivan Maillard

Authors
  1. Ashley R. Sandy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Morgan Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivan Maillard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivan Maillard .

Editor information

Editors and Affiliations

  1. Department of Dermatology, The Saarland University Hospital, Homburg, Germany

    Jörg Reichrath

  2. Department of Internal Medicine I, The Saarland University Hospital, Homburg, Germany

    Sandra Reichrath

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Sandy, A.R., Jones, M., Maillard, I. (2012). Notch Signaling and Development of the Hematopoietic System. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 727. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0899-4_6

Download citation

Publish with us

Policies and ethics

Search

Navigation