Experimental Hematology
Volume 35, Issue 5 , Pages 691-701 , May 2007

Are postnatal hemangioblasts generated by dedifferentiation from committed hematopoietic stem cells?

  • Gregor A. Prindull

      Affiliations

    • University of Göttingen, Göttingen, Germany
    • Corresponding Author InformationOffprint requests to: Gregor Prindull, M.D., Professor of Pediatric Hematology/Oncology, University of Göttingen, Department of Pediatrics, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
  • ,
  • Eitan Fibach

      Affiliations

    • Hebrew University Hospital Medical Center, Jerusalem, Israel

Received 7 August 2006 ,Revised 17 January 2007 ,Accepted 20 January 2007.

References 

  1. Quesenberry PJ, Dooner G, Colvin G, Abedi M. Stem cell biology and the plasticity polemic. Exp Hematol. 2005;33:389–394
  2. McConnell S, Kaznowski CE. Cell cycle dependence of laminar determination in developing neocortex. Science. 1991;254:282–285
  3. Quesenberry PJ, Colvin GA, Abedi M, et al. The marrow stem cell: the continuum. Bone Marrow Transplant. 2003;32:S19–S22
  4. Prindull G. Hypothesis: Cell plasticity, linking embryonal stem cells to adult stem cell reservoirs and metastatic cancer cells?. Exp Hematol. 2005;33:738–746
  5. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function?. Cell. 2001;105:829–841
  6. Sell S. Adult stem cell plasticity. Stem Cell Rev. 2005;1:1–7
  7. Orkin SH, Morrison SJ. Stem-cell competition. Nature. 2002;418:25–27
  8. Quesenberry PJ, Colvin GA, Lambert JF. The chiaroscuro stem cell: a unified stem cell theory. Blood. 2002;100:4266–4271
  9. Almeida-Porada G, Zanjani ED. A large animal noninjury model for study of human stem cell plasticity. Blood Cells Mol Dis. 2004;32:77–81
  10. Almeida-Porada G, Porada C, Zanjani ED. Plasticity of human stem cells in the fetal sheep model of human stem cell transplantation. Int J Hematol. 2004;79:1–6
  11. Prindull G. Maturation of cellular and humoral immunity during human embryonic development. Acta Paed Scand. 1974;63:607–615
  12. Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM. Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol. 2002;30:896–904
  13. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–49
  14. Becker PS, Nilsson SK, Li Z, et al. Adhesion receptor expression by hematopopietic cell lines and murine progenitors: modulation by cytokines and cell cycle status. Exp Hematol. 1999;27:533–541
  15. Lambert JF, Liu M, Colvin GA, et al. Marrow stem cells shift gene expression and engraftment phenotype with cell cycle transit. J Exp Med. 2003;197:1563–1572
  16. Prindull G, Zipori D. Environmental guidance of normal and tumor cell plasticity: epithelial mesenchymal transitions as a paradigm. Blood. 2004;103:2892–2899
  17. Prindull G. Spontaneous DNA synthesis of blood lymphoid cells in premature newborn infants, in older premature infants, and in full-term newborn infants. Z Kinderheilk. 1974;118:197–206
  18. Prindull G, Prindull B, Ron A, Yoffey JM. Cells in spontaneous DNA synthesis in cord blood of premature and full-term newborn infants. An autoradiographic study. J Pediatr. 1975;86:773–778
  19. Prindull G, Prindull B, Schröter W, Yoffey JM. Comparison of RNA and DNA synthesis, spontaneous and PHA induced, between blood lymphoid cells of newborn infants, older infants, and adults. A study by scintillation counting and by autoradiography. Eur J Pediatr. 1977;126:243–252
  20. Prindull G, Hespe A. Fetal blood borne myelo- and thrombopoietic stem cells in diffusion chambers. Eur J Pediatr. 1978;129:197–204
  21. Prindull G, Prindull B, Meulen v.d. N. Haermatopoietic stem cells (CFUc) in human cord blood. Acta Paediatr Scand. 1978;67:413–416.
  22. Prindull G, Albani M, Prindull B, Schröter W. Circulating hematopoietic stem cells in healthy and diseased pre-term infants. Scand J Haematol. 1980;25:268–274
  23. Prindull G, Gabriel M, Prindull B. Circulating myelopoietic stem cells (CFUc). High levels in healthy pre-term infants and reduced levels in sick pre-term infants. A study by methylcellulose cultures with the addition of exogenous colony stimulating factor (CSF). Blut. 1981;43:109–111
  24. Prindull G, Ben-Ishay Z, Gabriel M, Prindull B, Schröter W. A comparison of spontaneous and CSA added CFU-GM colony formation in healthy, sick, and hypotrophic pre-term infants. Blut. 1982;45:167–170
  25. Prindull G, Prindull B, Kiekenap R, Markus B. Radiosensitivity of hematopoietic stem cells (DCPC and CFU-GM) from cord blood. Scand J Haematol. 1983;31:229–234
  26. Prindull G. Early embryonal/fetal lymphopoietic ontogeny and leukemogenesis. Ann Hematol. 1991;63:291–296
  27. Peled T, Glukhman E, Hasson N, et al. Chelatable cellular copper modulates differentiation and self-renewal of cord blood–derived hematopoietic progenitor cells. Exp Hematol. 2005;33:1092–1100
  28. Peled T, Landau E, Mandel E, et al. Linear polyamine copper chelator tetraethylenepentamine augments long-term ex vivo expansion of cord blood–derived CD34+ cells and increases their engraftment potential in NOD/SCID mice. Exp Hematol. 2004;32:547–555
  29. Peled T, Landau E, Prus E, Treves AJ, Nagler A, Fibach E. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood–derived CD34+ cells. Br J Haematol. 2002;116:655–661
  30. Peled T, Mandel J, Goudsmid RN, et al. Pre-clinical development of cord blood–derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine. Cytotherapy. 2004;6:344–355
  31. Prus E, Chandraratna RA, Fibach E. Retinoic acid receptor antagonist inhibits CD38 antigen expression on human hematopoietic cells in vitro. Leuk Lymphoma. 2004;45:1025–1035
  32. Prus E, Peled T, Fibach E. The effect of tetraethylenepentamine, a synthetic copper chelating polyamine, on expression of CD34 and CD38 antigens on normal and leukemic hematopoietic cells. Leuk Lymphoma. 2004;45:583–589
  33. Jankovic V, Ciarrocchi A, Boccuni P, Benezra R, Nimer SU. Id1 regulates the choice of hematopoietic stem cells to self-renew or commit to differentiation. Blood. 2005;106:82a–83a(abstract #270)
  34. Niwa H, Burdon T, Chambers I, Smith A. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 1998;12:2048–2060
  35. Burdon T, Chambers I, Stracey C, Niwa H, Smith A. Signaling mechanisms regulating self-renewal and differentiation of pluripotent embryonic stem cells. Cells Tissues Organs. 1999;165:131–143
  36. Burdon T, Smith A, Savatier P. Signalling. Cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol. 2002;12:432–438
  37. Fraser ST, Ogawa M, Yu RT, Nishikawa S, Yoder MC, Nishikawa SI. Definitive hematopoietic commitment within the embryonic vascular endothelial-cadherin+ population. Exp Hematol. 2002;30:1070–1078
  38. Zipori D. Mesenchymal stem cells: Harnessing cell plasticity to tissue and organ repair. Blood Cells Mol Dis. 2004;33:211–215
  39. Zambidis ET, Peault B, Park TS, Bunz F, Civin CI. Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development. Blood. 2005;106:860–870
  40. Huber TL, Kouskoff V, Fehling HJ, Palis J, Keller G. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature. 2004;432:625–630
  41. Park C, Ma YD, Choi K. Evidence for the hemangioblast. Exp Hematol. 2005;33:965–970
  42. Willey S, Ayuso-Sacido A, Zhang H, et al. Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor. Blood. 2006;107:3122–3130
  43. Ferkowicz MJ, Yoder MC. Blood island formation: Longstanding observations and modern interpretations. Exp Hematol. 2005;33:1041–1047
  44. Drake CJ, Fleming PA. Vasculogenesis in the day 6.5 to 9.5 mouse embryo. Blood. 2000;95:1671–1679
  45. Kabrun N, Bühring HJ, Choi K, Ullrich A, Risau W, Keller G. Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development. 1997;124:2039–2048
  46. Schuh AC, Faloon P, Hu QL, Bhimani M, Choi K. In vitro hematopoietic and endothelial potential of flk-1−/− embryonic stem cells and embryos. Proc Natl Acad Sci U S A. 1999;96:2159–2164
  47. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376:62–66
  48. Joukov V, Kaipainen A, Jeltsch M, et al. Vascular endothelial growth factors VEGF-B and VEGF-C. J Cell Physiol. 1997;173:211–215
  49. Cerdan C, Rouleau A, Bhatiia M. VEGF-A165 augments erythropoietic development from human embryonic stem cells. Blood. 2004;103:2504–2512
  50. Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164–1169
  51. Fiedler W, Graeven U, Ergün S, et al. Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood. 1997;89:1870–1875
  52. Göthert JR, Gustin SE, van Eekelen JAM, Schmidt U, Hall MA, Jane SM. Genetically tagging endothelial cells in vivo: bone marrow–derived cells do not contribute to tumor endothelium. Blood. 2004;104:1769–1777
  53. Miyagi T, Takeno M, Nagafuchi H, Takahashi M, Suzuki N. Flk1+ cells derived from mouse embryonal stem cells reconstitute hematopoiesis in vivo in SCID mice. Exp Hematol. 2002;30:1444–1453
  54. Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G. A common precursor for hematopoietic and endothelial cells. Development. 1998;125:725–732
  55. Kennedy M, Firpo M, Choi K, et al. A common precursor for primitive erythropoiesis and definite haematopoiesis. Nature. 1997;386:488–493
  56. Palis J, Yoder MC. Yolk-sac hematopoiesis: The first blood cells of mouse and man. Exp Hematol. 2001;29:927–936
  57. Tavian M, Hallais MF, Péault B. Emergence of intraembryonic hematopoietic precursors in the pre-liver human embryo. Development. 1999;126:793–803
  58. Godin I, Cumano A. The hare and the tortoise: An embryonic haematopoietic race. Nat Rev Immunol. 2002;2:593–604
  59. Nishikawa SI, Nishikawa S, Hirashima M, Matsuyoshi N, Kodama H. Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hematopoietic lineages. Development. 1998;125:1747–1757
  60. Cortés F, Debacker C, Péault B, Labastie MC. Differential expression of KDR/VEGFR-2 and CD34 during mesoderm development of the early human embryo. Mech Dev. 1999;83:161–164
  61. Damert A, Miquerol L, Gertsenstein M, Risau W, Nagy A. Insufficient VEGF activity in yolk sac endoderm compromises hematopoietic and endothelial differentiation. Development. 2002;129:1881–1892
  62. Zippo A, DeRobertis A, Bardelli M, Galvagni F, Oliviero S. Identification of Flk-1 target genes in vasculogenesis: Pim-1 is required for endothelial and mural cell differentiation in vitro. Blood. 2004;103:4536–4544
  63. Shalaby F, Ho J, Stanford WL, et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell. 1997;89:981–990
  64. Keamey JB, Ambler CA, Monaco KA, Johnson N, Rapoport RG, Bautch VL. Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood. 2002;99:2397–2407
  65. Prindull G. Hemangioblasts representing a functional endothelio-hematopoietic entity in ontogeny, postnatal life, and CML neovasculogenesis. Stem Cell Rev. 2005;1:277–284
  66. Wang L, Menendez P, Cerdan C, Bhatia M. Hematopoietic development from human embryonic stem cell lines. Exp Hematol. 2005;33:987–996
  67. Yanagisawa KO, Fujimoto H, Urushihara H. Effects of the Brachyury (T) mutation on morphogenic movement in the mouse embryo. Dev Biol. 1981;87:242–248
  68. Wilson V, Manson L, Skarnes WC, Beddington RSP. The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation. Development. 1995;121:877–886
  69. Cogle CR, Scott EW. The hemangioblast: cradle to clinic. Exp Hematol. 2004;32:885–890
  70. Ema M, Faloon P, Zhang WJ, et al. Combinational effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Genes Dev. 2003;17:380–393
  71. Robertson SM, Kennedy M, Shannon JM, Keller G. A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1. Development. 2000;127:2447–2459
  72. Shivdasani RA, Mayer EL, Orkin SH. Absence of blood formation in mice lacking the T-cell leukemia oncoprotein tal-1/SCL. Nature. 1995;373:432–434
  73. Zhang WJ, Park C, Arentson E, Choi K. Modulation of hematopoietic and endothelial cell differentiation from mouse embryonic stem cells by different culture conditions. Blood. 2005;205:111–114
  74. Ernst P, Fisher JK, Avery W, Wade S, Foy D, Korsmeyer SJ. Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell. 2004;6:437–443
  75. Hadland BK, Huppert SS, Kanungo J, et al. A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development. Blood. 2004;104:3097–3105
  76. Robert-Moreno A, Espinosa L, de la Pompa JL, Bigas A. RBPjk dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development. 2005;132:1117–1126
  77. McGrath KE, Palis JP. Hematopoiesis in the yolk sac: More than meets the eye. Exp Hematol. 2005;33:1021–1028
  78. Robb L, Lyons I, Li R, et al. Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. Proc Natl Acad Sci U S A. 1995;92:7075–7079
  79. Visvader JE, Fujiwara Y, Orkin SH. Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular development. Genes Dev. 1998;12:473–479
  80. Jaffredo T, Nottingham W, Liddiard K, Bollerot K, Pouget C, de Bruijn M. From hemangioblast to hematopoietic stem cell: an endothelial connection?. Exp Hematol. 2005;33:1029–1040
  81. Hirai H, Samokhvalov IM, Fujimoto T, Nishikawa S, Imanishi J, Nishikawa SI. Involvement of Runx1 in the down-regulation of fetal liver kinase-1 expression during transition of endothelial cells to hematopoietic cells. Blood. 2005;106:1948–1955
  82. North TE, de Bruijn MFTR, Stacy T, et al. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity. 2002;16:661–672
  83. Lacaud G, Gore L, Kennedy M, et al. Runx1 is essential for hematopoietic commitment at the haemangioblast stage of development in vitro. Blood. 2002;100:458–466
  84. Cavalli G. Chromatin as a eukaryotic template of genetic information. Curr Opin Cell Biol. 2002;14:269–278
  85. Wolffe AP, Guschin D. Review: Chromatin structural features and targets that regulate transcription. J Struct Biol. 2000;129:102–122
  86. Guasconi V, Souidi M, Ait-Si-Ali S. Nuclear positioning, gene activity and cancer. Cancer Biol Ther. 2005;4:134–138
  87. Emery AEH, Dreifuss FE. Unusual type of benign X-linked muscular dystrophy. J Neurol Neurosurg Pyschiatr. 1966;29:338–342
  88. Simon JA, Tamkun JW. Programming off and on states in chromatin: Mechanisms of Polycomb and thrithorax group complexes. Curr Opin Genet Dev. 2002;12:210–218
  89. Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA. Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol. 1999;145:1119–1131
  90. Sjakste NI, Sjakste TG. Transcription factors and the nuclear matrix. Mol Biol. 2001;35:627–635
  91. Scheuermann MO, Murmann AE, Richter K, Görisch SM, Herrmann H, Lichter P. Characterization of nuclear compartments identified by ectopic markers in mammalian cells with distinctly different karyotype. Chromosoma. 2005;114:39–53
  92. Umanskaya ON, Bystritskiy AA, Razin SV. Chromosome rearrangement breakpoint clustering: The role of clonal selection. Mol Biol. 2005;39:313–320
  93. Stein GS, van Wijnen AJ, Stein J, Lian JB, Montecino M. Contributions of nuclear architecture to transcriptional control. Int Rev Cytol. 1995;162A:251–278
  94. Taniura H, Glass C, Gerace L. A chromatin binding site in the tail domain of nuclear lamins that interacts with core histones. J Cell Biol. 1995;131:33–44
  95. Oehr P. Proteomics as a tool for detection of nuclear matrix proteins and new biomarkers for screening of early tumor stages. Anticancer Res. 2003;23:805–812
  96. Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK, Spann TP. Nucelar lamins: Building blocks of nuclear architecture. Genes Dev. 2002;16:533–547
  97. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–45
  98. Görisch SM, Wachsmuth M, Tóth KF, Lichter P, Rippe K. Histone acetylation increases chromatin accessibility. J Cell Sci. 2005;118:5825–5834
  99. Boutanaev AM, Mikhaylova LM, Nurminsky DI. The pattern of chromosome folding in interphase is outlined by the linear gene density profile. Mol Cell Biol. 2005;25:8379–8386
  100. Chubb JR, Boyle S, Perry P, Bickmore WA. Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol. 2002;12:439–445
  101. Görisch SM, Lichter P, Rippe K. Mobility of multi-subunit complexes in the nucleus: Accessibility and dynamics of chromatin subcompartments. Histochem Cell Biol. 2005;123:217–228
  102. Francastel C, Schübeler D, Martin DIK, Groudine M. Nuclear compartmentalization and gene activity. Nat Rev Mol Cell Biol. 2000;1:137–143
  103. Dietzel S, Zolghadr K, Hepperger C, Belmont AS. Differential large-scale chromatin compaction and intranuclear positioning of transcribed versus non-transcribed transgene arrays containing β-globin regulatory sequences. J Cell Sci. 2004;117:4603–4614
  104. Cremer T, Kurz A, Zirbel R, et al. Role of chromosome territories in the functional compartmentalization of the cell nucleus. Cold Spring Harb Symp Quant Biol. 1993;58:777–792
  105. Tanabe H, Müller S, Neusser M, et al. Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc Natl Acad Sci U S A. 2002;99:4424–4429
  106. Scheuermann MO, Tajbakhsh J, Kurz A, Saracoglu K, Eils R, Lichter P. Topology of genes and nontranscribed sequences in human interphase nuclei. Exp Cell Res. 2004;301:266–279
  107. Eissenberg JC. Decisive factrors: A transcription activator can overcome heterochromatin silencing. BioEssays. 2001;23:767–771
  108. Yoffey JM, Courtice FC. Lymphatics, lymph and the lymphomyeloid complex. London, New York: Academic Press; 1970;
  109. Yoffey JM. Stem cell kinetics: correlation of in vivo and in vitro data. Exp Hematol. 1987;15:110–114
  110. Prindull G. Stem cells in the circulation. In:  Cohen P editors. Proc XI Int Congr Anat: Advances in the morphology of cells and tissues. New York: Alan R. Liss Inc; 1981;p. 243–247
  111. Akashi K, He X, Chen J, et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood. 2003;101:383–390
  112. Shen X, Xiao H, Ranallo R, Wu WH, Wu C. Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science. 2003;299:112–114
  113. Steger DJ, Haswell ES, Miller AL, Wente SR, O'Shea EK. Regulation of chromatin remodeling by inositol phosphates. Science. 2003;299:114–116
  114. Cosma MP, Tanaka T, Nasmyth K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally-regulated promotor. Cell. 1999;97:299–311
  115. Sudarsanam P, Winston F. The Swi/Snf family nucleosome-remodeling complexes and transcriptional control. Trends Genet. 2000;16:345–351
  116. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074–1080
  117. Zhang Y, Reinsberg D. Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails. Genes Dev. 2001;15:2343–2360
  118. Abu-Daya A, Steer WM, Trollope AF, et al. Zygotic nucleosome assembly protein-like 1 has a specific, non-cell autonomous role in hematopoiesis. Blood. 2005;106:514–520
  119. Hiragami K, Festenstein R. Heterochromatin protein 1: A pervasive controlling influence. Cell Mol Life Sci. 2005;62:2711–2726
  120. Grewal SIS, Elgin SCR. Heterochromatin: New possibilities for the inheritance of structure. Curr Opin Genet Dev. 2002;12:178–187
  121. Turner BM. Histone acetylation and epigenetic code. Bioessays. 2000;22:836–845
  122. Henikoff S, Ahmad K. Assembly of variant histones into chromatin. Ann Rev Cell Dev Biol. 2005;21:133–153
  123. LeBreton M, Cormier P, Bellé R, Mulner-Lorillon O, Morales J. Translational control during mitosis. Biochimie. 2005;87:805–811
  124. Eissenberg JC, Morris GD, Reuter G, Hartnett T. The heterochromatin-associated protein HP-1 is an essential protein in Drosophila with dosage-dependent effects on position-effect variegation. Genetics. 1992;131:345–352
  125. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293:1089–1093
  126. Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002;3:662–673
  127. Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature. 2001;410:116–120
  128. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21
  129. Tagoh H, Melnik S, Lefevre P, Chong S, Riggs AD, Bonifer C. Dynamic reorganization of chromatin structure and selective DNA demethylation prior to stable enhancer complex formation during differentiation of primary hematopoietic cells in vitro. Blood. 2004;103:2950–2955
  130. Yoder JA, Walsh CP, Bestor TH. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 1997;13:335–340
  131. Lee JH, Hart SRL, Skalnik DG. Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis. 2004;38:32–38
  132. Bannister AJ, Zegerman P, Partridge JF, et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 2001;410:120–124
  133. Jacob S, Moley KH. Gametes and embryo epigenetic reprogramming affect developmental outcome: implications for assisted reproductive technologies. Pediatr Res. 2005;58:437–446
  134. Schultz RM, Davus W, Stein P, Svoboda P. Reprogramming of gene expression during preimplantation development. J Exp Zool Mol Dev Evol. 1999;285:276–282
  135. Sjakste N, Sjakste T. Nuclear matrix proteins and hereditary diseases. Russ J Genet. 2005;41:221–226
  136. Linarez-Cruz G, Bruzzoni-Giovanelli H, Alvaro V, et al. p21WAF-1 reorganizes the nucleus in tumor suppression. Proc Natl Acad Sci U S A. 1998;95:1131–1135
  137. Jones PA. Overview of cancer epigenetics. Semin Hematol. 2005;42:S3–S8
  138. Issa JP. Age-related epigenetic changes and the immune system. Clin Immunol. 2003;109:103–108
  139. Müller H, Bracken AP, Vernell R, et al. E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev. 2001;15:267–285
  140. Bachman KE, Rountree MR, Baylin SB. Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J Biol Chem. 2001;276:32282–32287
  141. Jackson JP, Lindroth AM, Cao X, Jacobsen SE. Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature. 2002;416:556–560
  142. Trimarchi JM, Lees JA. Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol. 2002;3:11–20
  143. Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promotors. Nat Genet. 2000;25:338–342
  144. Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T. Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J. 2001;20:2536–2544
  145. MacCorkle RA, Tan TH. Mitogen-activated protein kinases in cell-cycle control. Cell Biochem Biophys. 2005;43:451–461
  146. Bartek J, Lukas J. Pathways governing G1/S transition and their response to DNA damage. FEBS Lett. 2001;490:117–122
  147. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13:1501–1512
  148. Martinsson HS, Starborg M, Erlandsson F, Zetterberg A. Single cell analysis of G1 checkpoints—The relationship between the restriction point and phosphorylation of pRB. Exp Cell Res. 2005;305:383–391
  149. Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev. 1998;12:2245–2262
  150. Bartkova J, Lukas J, Bartek J. Aberrations of the G1- and G1/S-regulating genes in human cancer. Prog Cell Cycle Res. 1997;3:211–220
  151. Sherr CJ. Cancer cell cycles. Science. 1996;274:1672–1677
  152. Narita M, Nunez S, Heard E, et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 2003;113:703–716
  153. Wikenheiser-Brokamp KA. Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol Life Sci. 2006;63:767–780
  154. Klar AJS. Propagating epigenetic states through meiosis: where Mendel's gene is more than a DNA moiety. Trends Genet. 1998;14:299–301
  155. Hannon GJ. RNA interference. Nature. 2002;418:244–251
  156. Erhardt S, Lyko F, Ainscough JFX, Surani MA, Paro R. Polycomb-group proteins are involved in silencing processes caused by a transgenic element from the murine imprinted H19/Igf2 region in Drosophila. Dev Genes Evol. 2003;213:336–344
  157. Li T, Vu TH, Ulaner GA, et al. IVF results in de novo DNA methylation and histone methylation at an Igf2-H19 imprinting epigenetic switch. Mol Hum Reprod. 2005;11:631–640
  158. Matzke MA, Birchler JA. RNAi-mediated pathways in the nucleus. Nat Rev Genet. 2005;6:24–35
  159. Tost J, Jammes H, Dupont JM, et al. Non-random, individual-specific methylation profiles are present at the sixth CTCF binding site in the human H19/IGF2 imprinting control region. Nucleic Acids Res. 2006;34:5438–5448
  160. Szabó PE, Han L, Hyo-Jung J, Mann JR. Mutagenesis in mice of the nuclear hormone receptor binding sites in the Ifg2/H19 imprinting control region. Cytogenet Genome Res. 2006;113:238–246
  161. Hagége H, Nasser R, Weber M, et al. The 3′ portion of the mouse H19 Imprinting Control Region is required for proper tissue-specific expression of the Igf2 gene. Cytogenet Genome Res. 2006;113:230–237
  162. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(suppl):245–254
  163. Engel N, Thorvaldsen JL, Bartolomei MS. CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus. Hum Mol Genet. 2006;15:2945–2954
  164. Kurukuti S, Tiwari VK, Tavoosidana G, et al. CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2. Proc Natl Acad Sci U S A. 2006;103:10684–10689
  165. Rosa AL, Wu YQ, Kwabi-Addo B, Coveler KJ, Sutton VR, Shaffer GL. Allele-specific methylation of functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32. Chromosome Res. 2005;13:809–818
  166. Thompson JR, Williams CJ. Genomic imprinting and assisted reproductive technology: Connections and potential risks. Sem Reprod Med. 2005;23:285–295
  167. Pool TB. An update on embryo culture for human assisted reproductive technology: Media, performance, and safety. Semin Reprod Med. 2005;23:309–318
  168. Galm O, Wilop S, Lüders C, et al. Clinical implications of aberrant DNA methylation patterns in acute myelogenous leukemia. Ann Hematol. 2005;84:39–46
  169. McHeyzer-Williams LJ, Malherbe LP, McHeyzer-Williams MG. Helper T cell–regulated B cell immunity. Curr Top Microbiol Immunol. 2006;311:59–83
  170. Tan JT, Surh CD. T cell memory. Curr Top Microbiol Immunol. 2006;311:85–115
  171. Tarlinton D. B-cell memory: Are subsets necessary?. Nat Rev Immunol. 2006;6:785–790
  172. Bruniquel RH, Schwartz RH. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol. 2003;4:235–240
  173. Lund AH, van Lohuizen M. Polycomb complexes and silencing mechanisms. Curr Opin Cell Biol. 2004;16:239–246
  174. Wolffe AP, Matzke MA. Epigenetics: Regulation through repression. Science. 1999;286:481–486
  175. Voncken JW, Schweizer D, Aagaard L, Sattler L, Jantsch MF, van Lohuizen M. Chromatin-association of the Polycomb group protein BMI1 is cell cycle–regulated and correlates with its phosphorylation status. J Cell Sci. 1999;112:4627–4639
  176. Issa JP. Epigenetic variation and human disease. J Nutr. 2002;132:2388S–2392S
  177. Paro R. Propagating memory of transcriptional states. Trends Genet. 1995;11:295–297
  178. Jackson M, Krassowska A, Gilbert N, et al. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol Cell Biol. 2004;24:8862–8871
  179. Tang X, Milyavsky M, Shats I, Erez N, Goldfinger N, Rotter V. Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene. 2004;23:5759–5769
  180. Viré E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439:871–874
  181. Vakoc CR, Mandat SA, Olenschock BA, Blobel GA. Histone H3 lysine methylation and HP1γ are associated with transcription elongation through mammalian chromatin. Blood. 2005;106(11, part1):493;Abstract #1734
  182. Byrne JA, Simonsson S, Western PS, Gurdon JB. Nuclei of adult mammalian somatic cells are directly reprogrammed to oct-4 stem cell gene expression by amphibian oocytes. Curr Biol. 2003;13:1206–1213
  183. Taranger CK, Noer A, Sorensen AL, Hakelien AM, Boquest AC, Collas P. Induction of dedifferentiation, genomewide transcriptional programming, and epigenetic reprogramming by extracts of carcinoma and embryonic stem cells. Mol Biol Cell. 2005;16:5719–5735
  184. Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122:947–956
  185. Landsverk HB, Hakelien AM, Küntziger T, Robl JM, Skalhegg BS, Collas P. Reprogrammed gene expression in a somatic cell-free extract. EMBO Rep. 2002;3:384–389
  186. Hakelien AM, Landsverk HB, Robl JM, Skalhegg BS, Collas P. Reprogramming fibroblasts to express T-cell functions using cell extracts. Nat Biotechnol. 2002;20:460–466
  187. Hakelien AM, Gaustad KG, Taranger CK, Skalhegg BS, Küntziger T, Collas P. Long-term in vitro, cell-type-specific genome-wide reprogramming of gene expression. Exp Cell Res. 2005;309:32–47
  188. O'Malley K, Scott EW. Stem cell fusion confusion. Exp Hematol. 2004;32:131–134
  189. Cowan CA, Atienza J, Melton DA, Eggan K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science. 2005;309:1369–1373
  190. Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 2002;416:542–545
  191. Pells S, Di Domenico AI, Gallagher EJ, McWhir J. Multipotentiality of neuronal cells after spontaneous fusion with embryonic stem cells and nuclear reprogramming in vitro. Cloning Stem Cells. 2002;4:331–338
  192. Ying QL, Nichols J, Evans EP, Smith AG. Changing potency by spontaneous fusion. Nature. 2002;416:545–548
  193. Weimann JM, Johansson CB, Trejo A, Blau HM. Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant. Nat Cell Biol. 2003;5:959–966
  194. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, et al. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 2003;425:968–973
  195. Giguere L, Morais R. On suppression of tumorigenesis in hybrid and cybrid mouse cells. Somatic Cell Genet. 1981;7:457–471
  196. Anderson MJ, Stanbridg EJ. Tumor suppressor genes studied by cell hybridization and chromosome transfer. FASEB J. 1993;7:826–833
  197. Cibelli JB, Stice SL, Golueke PJ, et al. Transgenic bovine chimeric offspring produced from somatic cell–derived stem-like cells. Nat Biotechnol. 1998;16:642–646
  198. Wakayama T, Tabar V, Rodriguez I, Perry ACF, Studer L, Mombaerts P. Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science. 2001;292:740–743
  199. Munsie MJ, Michalska AE, O'Brien CM, Trounson AO, Pera MF, Mountford PS. Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol. 2000;10:989–992
  200. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KHS. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385:810–813
  201. Wilmut I, Beaujean N, de Sousa PA, et al. Somatic cell nuclear transfer. Nature. 2002;419:583–586
  202. Gurdon JB, Byrne JA. The first half-century of nuclear transplantation. Proc Natl Acad Sci U S A. 2003;100:8048–8052
  203. Santos F, Zakhartchenko V, Stojkovic M, et al. Epigenetic marking correlates with developmental potential in cloned bovine preimplantation embryos. Curr Biol. 2003;13:1116–1121
  204. Humpherys D, Eggan K, Akutsu H, et al. Epigenetic instability in ES cells and cloned mice. Science. 2001;293:95–97
  205. Gao S, Latham KE. Maternal and environmental factors in early cloned embryo development. Cytogenet Genome Res. 2004;105:279–284
  206. Tamada H, Kikyo N. Nuclear reprogramming in mammalian somatic cell nuclear cloning. Cytogenet Genome Res. 2004;105:285–291
  207. Campbell KHS, Loi P, Otaegui PJ, Wilmut I. Cell cycle co-ordination in embryo cloning by nuclear transfer. Rev Reprod. 1996;1:40–46
  208. Bloor DJ, Metcalfe AD, Rutherford A, Brison DR, Kimber SJ. Expression of cell adhesion molecules during human preimplantation embryo development. Mol Hum Reprod. 2002;8:237–245
  209. Kidder GM, Winterhager E. Intercellular communication in preimplantation development: the role of gap junctions. Front Biosci. 2001;6:D731–D736
  210. Houghton FD, Barr KJ, Walter G, et al. Functional significance of gap junctional coupling in preimplantation development. Biol Reprod. 2002;66:1403–1412
  211. Perez-Pomares JM, Munoz-Chapuli E. Epithelial-mesenchymal transitions: A mesodermal cell strategy for evolutive innovation in metazoans. Anat Rec. 2002;268:343–351
  212. Yokoyama K, Kamata N, Fujimoto R, et al. Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinoma. Int J Oncol. 2003;22:891–898
  213. Gotzmann J, Mikula M, Eger A, et al. Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis. Mutat Res. 2004;566:9–20
  214. Brabletz T, Hlubek F, Spaderna S, et al. Invasion and metastasis in colorectal cancer: Epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and β-catenin. Cells Tissues Organs. 2005;179:56–65
  215. Kirchner T, Müller S, Hattori T, et al. Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis. Virch Arch. 2001;439:512–522
  216. Ougolkov AV, Fernandez-Zapico ME, Bilim VN, Smyrk TC, Chari ST, Billadeau DD. Aberrant nuclear accumulation of glycogen synthase kinase-3β in human pancreatic cancer: Association with kinase activity and tumor dedifferentiation. Clin Cancer Res. 2006;12:5074–5081
  217. Draisma G, Postma R, Schröder FH, van der Kwast TH, de Koning HJ. Gleason score, age and screening: Modeling dedifferentiation in prostate cancer. Int J Cancer. 2006;119:2366–2371
  218. Peinado H, Portillo F, Cano A. Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol. 2004;48:365–375
  219. Hay ED. An overview of epithelio-mesenchymal transformation. Acta Anat. 1995;154:8–20
  220. Vandewalle C, Comijn J, De Craene B, et al. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acid Res. 2005;33:6566–6578
  221. Tester AM, Ruangpanit N, Anderson RL, Thompson EW. MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial-mesenchymal transition traits. Clin Exp Metastasis. 2001;18:553–560
  222. Cai J, Weiss ML, Rao MS. In search of “stemness.”. Exp Hematol. 2004;32:585–598
  223. Joshi CV, Enver T. Plasticity revisited. Curr Opin Cell Biol. 2002;14:749–755
  224. Walder S, Zhang F, Ferretti P. Upregulation of stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord. Dev Genes Evol. 2003;213:625–630
  225. McGann CJ, Odelberg SJ, Keating MT. Mammalian myotube dedifferentiation induced by newt regeneration extract. Proc Natl Acad Sci U S A. 2001;98:13699–13704
  226. Velloso CP, Simon A, Brockes JP. Mammalian postmitotic nuclei reenter the cell cycle after serum stimulation in newt/mouse hybrid myotubes. Curr Biol. 2001;11:855–858
  227. Jögi A, Ora I, Nilsson H, et al. Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci U S A. 2002;99:7021–7026
  228. Helczynska K, Kronblad A, Jögi A, et al. Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ. Cancer Res. 2003;63:1441–1444
  229. Lal A, Peters H, Croix BS, et al. Transcriptional response to hypoxia in human tumors. J Nat Cancer Inst. 2001;93:1337–1343
  230. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3:721–732
  231. Kondo T, Raff M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science. 2000;289:1754–1757
  232. Kang SK, Park JB, Cha SH. Multipotent, dedifferentiated cancer stem-like cells from brain gliomas. Stem Cells Dev. 2006;15:423–435
  233. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002;297:2256–2259
  234. Castro RE, Jackson KA, Goodell MA, Robertson CS, Liu H, Shine HD. Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science. 2002;297:1299–1302
  235. Bailey AS, Jiang S, Afentoulis M, et al. Transplanted adult hematopoietic stem cells differentiate into functional endothelial cells. Blood. 2004;103:13–19
  236. Grant MB, May WS, Caballero S, et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med. 2002;8:607–612
  237. Fang B, Zheng C, Liao L, et al. Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics. Blood. 2005;105:2733–2740
  238. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7:430–436
  239. Pelosi E, Valtieri M, Coppola S, et al. Identification of the hemangioblast in postnatal life. Blood. 2002;100:3203–3208
  240. Cogle CR, Wainman DA, Jorgensen ML, Gutherie SM, Mames RN, Scott EW. Adult human hematopoietic cells provide functional hemangioblast activity. Blood. 2004;103:133–135
  241. Loges S, Fehse B, Brockmann MA, et al. Identification of the adult human hemangioblast. Stem Cells Dev. 2004;13:229–242
  242. Ziegler BL, Valtieri M, Almeida-Porada G, et al. KDR receptor: A key marker defining hematopoietic stem cells. Science. 1999;285:1553–1558
  243. Zhao Y, Glesne D, Huberman E. A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc Natl Acad Sci U S A. 2003;100:2426–2431
  244. Minasi MG, Riminucci M, DeAngelis L, et al. The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues. Development. 2002;129:2773–2783
  245. Bailey AS, Willenbring H, Jiang S, et al. Myeloid lineage progenitors give rise to vascular endothelium. Proc Natl Acad Sci U S A. 2006;103:13156–13161
  246. Colvin GA, Lambert JF, Moore BE, et al. Intrinsic hematopoietic stem cell/progenitor plasticity: Inversions. J Cell Physiol. 2004;199:20–31
  247. Kögler G, Sensken S, Airey JA, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med. 2004;200:123–135

PII: S0301-472X(07)00059-8

doi: 10.1016/j.exphem.2007.01.047

Experimental Hematology
Volume 35, Issue 5 , Pages 691-701 , May 2007