Stem Cell Reviews

, Volume 4, Issue 4, pp 283–292 | Cite as

Role of Gap Junctions in Embryonic and Somatic Stem Cells

  • Raymond C. B. Wong
  • Martin F. Pera
  • Alice Pébay
Article

Abstract

Stem cells provide an invaluable tool to develop cell replacement therapies for a range of serious disorders caused by cell damage or degeneration. Much research in the field is focused on the identification of signals that either maintain stem cell pluripotency or direct their differentiation. Understanding how stem cells communicate within their microenvironment is essential to achieve their therapeutic potentials. Gap junctional intercellular communication (GJIC) has been described in embryonic stem cells (ES cells) and various somatic stem cells. GJIC has been implicated in regulating different biological events in many stem cells, including cell proliferation, differentiation and apoptosis. This review summarizes the current understanding of gap junctions in both embryonic and somatic stem cells, as well as their potential role in growth control and cellular differentiation.

Keywords

Somatic stem cells Neural stem cells Hematopoietic stem cells Mesenchymal stem cells Embryonic stem cells Gap junctions Gap junctional intercellular communication 

Abbreviations

α-GA

α-glycyrrhetinic acid

BMP

Bone morphogenetic protein

ES cells

Embryonic stem cells

HSC

Hematopoietic stem cells

MSC

Mesenchymal stem cells

GJIC

Gap junctional intercellular communication

hESC

Human embryonic stem cells

mESC

Mouse embryonic stem cells

PDGF

Platelet-derived growth factor

S1P

Sphingosine-1-phosphate

Notes

Acknowledgements

This work was supported by the California Institute of Regenerative Medicine, the University of Melbourne and the National Health and Medical Research Council of Australia (NHMRC 454723).

References

  1. 1.
    Alexander, D. B., & Goldberg, G. S. (2003). Transfer of biologically important molecules between cells through gap junction channels. Current Medicinal Chemistry, 10(19), 2045–2058.PubMedGoogle Scholar
  2. 2.
    Assou, S., Lecarrour, T., et al. (2007). A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas. Stem Cells, 25, 961–973.PubMedGoogle Scholar
  3. 3.
    Avanzo, J. L., Mesnil, M., et al. (2004). Increased susceptibility to urethane-induced lung tumors in mice with decreased expression of connexin43. Carcinogenesis, 25(10), 1973–1982.PubMedGoogle Scholar
  4. 4.
    Bani-Yaghoub, M., Bechberger, J. F., et al. (1997). Reduction of connexin43 expression and dye-coupling during neuronal differentiation of human NTera2/clone D1 cells. Journal of Neuroscience Research, 49(1), 19–31.PubMedGoogle Scholar
  5. 5.
    Becker, D. L., Evans, W. H., et al. (1995). Functional analysis of amino acid sequences in connexin43 involved in intercellular communication through gap junctions. Journal of Cell Science, 108(Pt 4), 1455–1467.PubMedGoogle Scholar
  6. 6.
    Belliveau, D. J., Bechberger, J. F., et al. (1997). Differential expression of gap junctions in neurons and astrocytes derived from P19 embryonal carcinoma cells. Developmental Genetics, 21(3), 187–200.PubMedGoogle Scholar
  7. 7.
    Beqqali, A., Kloots, J., et al. (2006). Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells, 24(8), 1956–1967.PubMedGoogle Scholar
  8. 8.
    Bernacki, S. H., Wall, M. E., et al. (2008). Isolation of human mesenchymal stem cells from bone and adipose tissue. Methods in Cell Biology, 86, 257–278.PubMedGoogle Scholar
  9. 9.
    Bevilacqua, A., Loch-Caruso, R., et al. (1989). Abnormal development and dye coupling produced by antisense RNA to gap junction protein in mouse preimplantation embryos. Proceedings of National Academy of Sciences of United States of America, 86(14), 5444–5448.Google Scholar
  10. 10.
    Bhattacharya, B., Cai, J., et al. (2005). Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies. BMC Developmental Biology, 5, 22.PubMedGoogle Scholar
  11. 11.
    Bhattacharya, B., Miura, T., et al. (2004). Gene expression in human embryonic stem cell lines: unique molecular signature. Blood, 103(8), 2956–2964.PubMedGoogle Scholar
  12. 12.
    Bloor, D. J., Wilson, Y., et al. (2004). Expression of connexins in human preimplantation embryos in vitro. Reproductive Biology and Endocrinology, 2, 25.PubMedGoogle Scholar
  13. 13.
    Boyer, L. A., Lee, T. I., et al. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 122(6), 947–956.PubMedGoogle Scholar
  14. 14.
    Cai, J., Cheng, A., et al. (2004). Membrane properties of rat embryonic multipotent neural stem cells. Journal of Neurochemistry, 88(1), 212–226.PubMedGoogle Scholar
  15. 15.
    Carpenter, M. K., Rosler, E. S., et al. (2004). Properties of four human embryonic stem cell lines maintained in a feeder-free culture system. Developmental Dynamics, 229(2), 243–258.PubMedGoogle Scholar
  16. 16.
    Chang, C. C., Trosko, J. E., et al. (1987). Contact insensitivity of a subpopulation of normal human fetal kidney epithelial cells and of human carcinoma cell lines. Cancer Research, 47(6), 1634–1645.PubMedGoogle Scholar
  17. 17.
    Cheng, A., Tang, H., et al. (2004). Gap junctional communication is required to maintain mouse cortical neural progenitor cells in a proliferative state. Developments in Biologicals, 272(1), 203–216.Google Scholar
  18. 18.
    Chung, Y., Klimanskaya, I., et al. (2008). Human embryonic stem cell lines generated without embryo destruction. Cell Stem Cell, 2(2), 113–117.PubMedGoogle Scholar
  19. 19.
    Dahl, E., Winterhager, E., et al. (1996). Expression of the gap junction proteins connexin31 and connexin43 correlates with communication compartments in extraembryonic tissues and in the gastrulating mouse embryo, respectively. Journal of Cell Science, 109(Pt 1), 191–197.PubMedGoogle Scholar
  20. 20.
    Dale, B., Gualtieri, R., et al. (1991). Intercellular communication in the early human embryo. Molecular Reproduction and Development, 29(1), 22–28.PubMedGoogle Scholar
  21. 21.
    Davies, T. C., Barr, K. J., et al. (1996). Multiple members of the connexin gene family participate in preimplantation development of the mouse. Developmental Genetics, 18(3), 234–243.PubMedGoogle Scholar
  22. 22.
    De Maio, A., Vega, V., et al. (2002). Gap junctions, homeostasis, and injury. Journal of Cellular Physiology, 191(3), 269–282.PubMedGoogle Scholar
  23. 23.
    Dowling-Warriner, C. V., & Trosko, J. E. (2000). Induction of gap junctional intercellular communication, connexin43 expression, and subsequent differentiation in human fetal neuronal cells by stimulation of the cyclic AMP pathway. Neuroscience, 95(3), 859–868.PubMedGoogle Scholar
  24. 24.
    Duval, N., Gomes, D., et al. (2002). Cell coupling and Cx43 expression in embryonic mouse neural progenitor cells. Journal of Cell Science, 115(Pt 16), 3241–3251.PubMedGoogle Scholar
  25. 25.
    Ebihara, L. (2003). New roles for connexons. News in Physiological Sciences, 18, 100–103.Google Scholar
  26. 26.
    Egashira, K., Nishii, K., et al. (2004). Conduction abnormality in gap junction protein connexin45-deficient embryonic stem cell-derived cardiac myocytes. The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology, 280(2), 973–979.PubMedGoogle Scholar
  27. 27.
    Elfgang, C., Eckert, R., et al. (1995). Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. Journal of Cell Biology, 129(3), 805–817.PubMedGoogle Scholar
  28. 28.
    Engel, A., & Muller, D. J. (2000). Observing single biomolecules at work with the atomic force microscope. Nature Structural Biology, 7(9), 715–718.PubMedGoogle Scholar
  29. 29.
    Enver, T., Soneji, S., et al. (2005). Cellular differentiation hierarchies in normal and culture-adapted human embryonic stem cells. Human Molecular Genetics, 14(21), 3129–3140.PubMedGoogle Scholar
  30. 30.
    Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.PubMedGoogle Scholar
  31. 31.
    Evans, W. H., De Vuyst, E., et al. (2006). The gap junction cellular internet: connexin hemichannels enter the signalling limelight. Biochemical Journal, 397(1), 1–14.PubMedGoogle Scholar
  32. 32.
    Gage, F. H. (2000). Mammalian neural stem cells. Science, 287(5457), 1433–1438.PubMedGoogle Scholar
  33. 33.
    Giepmans, B. N. (2004). Gap junctions and connexin-interacting proteins. Cardiovascular Research, 62(2), 233–245.PubMedGoogle Scholar
  34. 34.
    Goodall, H., & Maro, B. (1986). Major loss of junctional coupling during mitosis in early mouse embryos. Journal of Cell Biology, 102(2), 568–575.PubMedGoogle Scholar
  35. 35.
    Goodenough, D. A., Goliger, J. A., et al. (1996). Connexins, connexons, and intercellular communication. Annual Reviews of Biochemical, 65, 475–502.Google Scholar
  36. 36.
    Goodenough, D. A., & Paul, D. L. (2003). Beyond the gap: functions of unpaired connexon channels. Nature Reviews. Molecular Cell Biology, 4(4), 285–294.PubMedGoogle Scholar
  37. 37.
    Hardy, K., Warner, A., et al. (1996). Expression of intercellular junctions during preimplantation development of the human embryo. Molecular Human Reproduction, 2(8), 621–632.PubMedGoogle Scholar
  38. 38.
    Hirabayashi, Y., Yoon, B. I., et al. (2007a). Membrane channel connexin 32 maintains Lin(-)/c-kit(+) hematopoietic progenitor cell compartment: analysis of the cell cycle. Journal of Membrane Biology, 217(1–3), 105–113.PubMedGoogle Scholar
  39. 39.
    Hirabayashi, Y., Yoon, B. I., et al. (2007b). Protective role of connexin 32 in steady-state hematopoiesis, regeneration state, and leukemogenesis. Experimental Biology and Medicine (Maywood), 232(5), 700–712.Google Scholar
  40. 40.
    Holland, M. S., Tai, M. H., et al. (2003). Isolation and differentiation of bovine mammary gland progenitor cell populations. American Journal of Veterinary Research, 64(4), 396–403.PubMedGoogle Scholar
  41. 41.
    Houghton, F. D. (2005). Role of gap junctions during early embryo development. Reproduction, 129(2), 129–135.PubMedGoogle Scholar
  42. 42.
    Houghton, F. D., Barr, K. J., et al. (2002). Functional significance of gap junctional coupling in preimplantation development. Biology of Reproduction, 66(5), 1403–1412.PubMedGoogle Scholar
  43. 43.
    Huang, Y. J., Maruyama, Y., et al. (2007). The role of pannexin 1 hemichannels in ATP release and cell–cell communication in mouse taste buds. Proceedings of National Academy of Sciences of the United State of America, 104(15), 6436–6441.Google Scholar
  44. 44.
    Huettner, J. E., Lu, A., et al. (2006). Gap junctions and connexon hemichannels in human embryonic stem cells. Stem Cells, 24(7), 1654–1667.PubMedGoogle Scholar
  45. 45.
    Kalimi, G. H., & Lo, C. W. (1988). Communication compartments in the gastrulating mouse embryo. Journal of Cell Biology, 107(1), 241–255.PubMedGoogle Scholar
  46. 46.
    Kalimi, G. H., & Lo, C. W. (1989). Gap junctional communication in the extraembryonic tissues of the gastrulating mouse embryo. Journal of Cell Biology, 109(6 Pt 1), 3015–3026.PubMedGoogle Scholar
  47. 47.
    Kao, C. Y., Nomata, K., et al. (1995). Two types of normal human breast epithelial cells derived from reduction mammoplasty: phenotypic characterization and response to SV40 transfection. Carcinogenesis, 16(3), 531–538.PubMedGoogle Scholar
  48. 48.
    Kiel, M. J., He, S., et al. (2007). Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature, 449(7159), 238–242.PubMedGoogle Scholar
  49. 49.
    King, T. J., Fukushima, L. H., et al. (2000). Correlation between growth control, neoplastic potential and endogenous connexin43 expression in HeLa cell lines: implications for tumor progression. Carcinogenesis, 21(2), 311–315.PubMedGoogle Scholar
  50. 50.
    Knoblich, J. A. (2008). Mechanisms of asymmetric stem cell division. Cell, 132(4), 583–597.PubMedGoogle Scholar
  51. 51.
    Krutovskikh, V. A., Yamasaki, H., et al. (1998). Inhibition of intrinsic gap-junction intercellular communication and enhancement of tumorigenicity of the rat bladder carcinoma cell line BC31 by a dominant-negative connexin 43 mutant. Molecular Carcinogenesis, 23(4), 254–261.PubMedGoogle Scholar
  52. 52.
    Krysko, D. V., Leybaert, L., et al. (2005). Gap junctions and the propagation of cell survival and cell death signals. Apoptosis, 10(3), 459–469.PubMedGoogle Scholar
  53. 53.
    Kumar, N. M., & Gilula, N. B. (1996). The gap junction communication channel. Cell, 84(3), 381–388.PubMedGoogle Scholar
  54. 54.
    Kwak, B. R., & Jongsma, H. J. (1996). Regulation of cardiac gap junction channel permeability and conductance by several phosphorylating conditions. Molecular and Cellular Biochemistry, 157(1–2), 93–99.PubMedGoogle Scholar
  55. 55.
    Lai, C. P., Bechberger, J. F., et al. (2007). Tumor-suppressive effects of pannexin 1 in C6 glioma cells. Cancer Research, 67(4), 1545–1554.PubMedGoogle Scholar
  56. 56.
    Laird, D. W. (2005). Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation. Biochimica et Biophysica Acta, 1711(2), 172–182.PubMedGoogle Scholar
  57. 57.
    Lampe, P. D., & Lau, A. F. (2004). The effects of connexin phosphorylation on gap junctional communication. International Journal of Biochemistry & Cell Biology, 36(7), 1171–1186.Google Scholar
  58. 58.
    Lee, S., Gilula, N. B., et al. (1987). Gap junctional communication and compaction during preimplantation stages of mouse development. Cell, 51(5), 851–860.PubMedGoogle Scholar
  59. 59.
    Lin, T. M., Chang, H. W., et al. (2007). Isolation and identification of mesenchymal stem cells from human lipoma tissue. Biochemical and Biophysical Research Communications, 361(4), 883–889.PubMedGoogle Scholar
  60. 60.
    Litvin, O., Tiunova, A., et al. (2006). What is hidden in the pannexin treasure trove: the sneak peek and the guesswork. Journal of Cellular and Molecular Medicine, 10(3), 613–634.PubMedGoogle Scholar
  61. 61.
    Liu, Y., Shin, S., et al. (2006). Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Developmental Biology, 6, 20.PubMedGoogle Scholar
  62. 62.
    Lo, C. W. (1996). The role of gap junction membrane channels in development. Journal of Bioenergetics and Biomembranes, 28(4), 379–385.PubMedGoogle Scholar
  63. 63.
    Lo, C. W., & Gilula, N. B. (1979a). Gap junctional communication in the post-implantation mouse embryo. Cell, 18(2), 411–422.PubMedGoogle Scholar
  64. 64.
    Lo, C. W., & Gilula, N. B. (1979b). Gap junctional communication in the preimplantation mouse embryo. Cell, 18(2), 399–409.PubMedGoogle Scholar
  65. 65.
    Loewenstein, W. R. (1979). Junctional intercellular communication and the control of growth. Biochimica et Biophysica Acta, 560(1), 1–65.PubMedGoogle Scholar
  66. 66.
    Loewenstein, W. R., & Kanno, Y. (1966). Intercellular communication and the control of tissue growth: lack of communication between cancer cells. Nature, 209(5029), 1248–1249.PubMedGoogle Scholar
  67. 67.
    Loewenstein, W. R., & Kanno, Y. (1967). Intercellular communication and tissue growth. I. Cancerous growth. Journal of Cell Biology, 33(2), 225–234.PubMedGoogle Scholar
  68. 68.
    Loewenstein, W. R., & Rose, B. (1992). The cell–cell channel in the control of growth. Seminars in Cell & Biology, 3(1), 59–79.CrossRefGoogle Scholar
  69. 69.
    Martin, G. R. (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proceedings of National Academy of Sciences of the United State of America, 78(12), 7634–7638.Google Scholar
  70. 70.
    Martin, P. E., & Evans, W. H. (2004). Incorporation of connexins into plasma membranes and gap junctions. Cardiovascular Research, 62(2), 378–387.PubMedGoogle Scholar
  71. 71.
    Matic, M., Evans, W. H., et al. (2002). Epidermal stem cells do not communicate through gap junctions. Journal of Investigative Dermatology, 118(1), 110–116.PubMedGoogle Scholar
  72. 72.
    Matic, M., Petrov, I. N., et al. (1997). Stem cells of the corneal epithelium lack connexins and metabolite transfer capacity. Differentiation, 61(4), 251–260.PubMedGoogle Scholar
  73. 73.
    McCulloch, E. A., & Till, J. E. (2005). Perspectives on the properties of stem cells. Natural Medicines, 11(10), 1026–1028.Google Scholar
  74. 74.
    Melton, D. a., & Cowan, C. (2004). ‘Stemness’: Definitions, criteria and standards. In R. Lanza, J. Gearhart, B. Hogan, D. Melton, R. Pedersen, J. Thomson, & M. West (Eds.), Handbook of stem cells, Vol. 1. Amsterdam: Elsevier.Google Scholar
  75. 75.
    Mesnil, M., Crespin, S., et al. (2005). Defective gap junctional intercellular communication in the carcinogenic process. Biochimica et Biophysica Acta, 1719(1–2), 125–145.PubMedGoogle Scholar
  76. 76.
    Mesnil, M., & Yamasaki, H. (2000). Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: role of gap-junctional intercellular communication. Cancer Research, 60(15), 3989–3999.PubMedGoogle Scholar
  77. 77.
    Mimeault, M., & Batra, S. K. (2006). Concise review: recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells, 24(11), 2319–2345.PubMedGoogle Scholar
  78. 78.
    Montecino-Rodriguez, E., Leathers, H., et al. (2000). Expression of connexin 43 (Cx43) is critical for normal hematopoiesis. Blood, 96(3), 917–924.PubMedGoogle Scholar
  79. 79.
    Moreno, A. P. (2005). Connexin phosphorylation as a regulatory event linked to channel gating. Biochimica et Biophysica Acta, 1711(2), 164–171.PubMedGoogle Scholar
  80. 80.
    Neijssen, J., Herberts, C., et al. (2005). Cross-presentation by intercellular peptide transfer through gap junctions. Nature, 434(7029), 83–88.PubMedGoogle Scholar
  81. 81.
    Nishi, M., Kumar, N. M., et al. (1991). Developmental regulation of gap junction gene expression during mouse embryonic development. Developments in Biologicals, 146(1), 117–130.Google Scholar
  82. 82.
    Orford, K. W., & Scadden, D. T. (2008). Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nature Reviews. Genetics, 9(2), 115–128.PubMedGoogle Scholar
  83. 83.
    Oviedo, N. J., & Levin, M. (2007). smedinx-11 is a planarian stem cell gap junction gene required for regeneration and homeostasis. Development, 134(17), 3121–3131.PubMedGoogle Scholar
  84. 84.
    Oyamada, M., Oyamada, Y., et al. (2005). Regulation of connexin expression. Biochimica et Biophysica Acta, 1719(1–2), 6–23.PubMedGoogle Scholar
  85. 85.
    Oyamada, Y., Komatsu, K., et al. (1996). Differential regulation of gap junction protein (connexin) genes during cardiomyocytic differentiation of mouse embryonic stem cells in vitro. Experimental Cell Research, 229(2), 318–326.PubMedGoogle Scholar
  86. 86.
    Panchin, Y., Kelmanson, I., et al. (2000). A ubiquitous family of putative gap junction molecules. Current Biology, 10(13), R473–R474.PubMedGoogle Scholar
  87. 87.
    Panchin, Y. V. (2005). Evolution of gap junction proteins—the pannexin alternative. Journal of Experimental Biology, 208(Pt 8), 1415–1419.PubMedGoogle Scholar
  88. 88.
    Parekkadan, B., Berdichevsky, Y., et al. (2008). Cell–cell interaction modulates neuroectodermal specification of embryonic stem cells. Neuroscience Letters, 438(2), 190–195.PubMedGoogle Scholar
  89. 89.
    Pebay, A., Wong, R. C., et al. (2005). Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in the maintenance of human embryonic stem cells. Stem Cells, 23(10), 1541–1548.PubMedGoogle Scholar
  90. 90.
    Penn, R. D. (1966). Ionic communication between liver cells. Journal of Cell Biology, 29(1), 171–174.PubMedGoogle Scholar
  91. 91.
    Pera, M. F., Reubinoff, B., et al. (2000). Human embryonic stem cells. Journal of Cell Science, 113(Pt 1), 5–10.PubMedGoogle Scholar
  92. 92.
    Phinney, D. G., & Prockop, D. J. (2007). Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views. Stem Cells, 25(11), 2896–2902.PubMedGoogle Scholar
  93. 93.
    Pittenger, M. F., Mackay, A. M., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–147.PubMedGoogle Scholar
  94. 94.
    Ploemacher, R. E., Mayen, A. E., et al. (2000). Hematopoiesis: gap junction intercellular communication is likely to be involved in regulation of stroma-dependent proliferation of hemopoietic stem cells. Hematology, 5(2), 133–147.PubMedGoogle Scholar
  95. 95.
    Qin, H., Shao, Q., et al. (2002). Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication. Journal of Biological Chemistry, 277(32), 29132–29138.PubMedGoogle Scholar
  96. 96.
    Reubinoff, B. E., Pera, M. F., et al. (2000). Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature Biotechnology, 18(4), 399–404.PubMedGoogle Scholar
  97. 97.
    Revel, J. P., & Karnovsky, M. J. (1967). Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. Journal of Cell Biology, 33(3), C7–C12.PubMedGoogle Scholar
  98. 98.
    Richards, M., Tan, S. P., et al. (2004). The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells, 22(1), 51–64.PubMedGoogle Scholar
  99. 99.
    Rosendaal, M., Green, C. R., et al. (1994). Up-regulation of the connexin43+ gap junction network in haemopoietic tissue before the growth of stem cells. Journal of Cell Science, 107(Pt 1), 29–37.PubMedGoogle Scholar
  100. 100.
    Rosendaal, M., Mayen, A., et al. (1997). Does transmembrane communication through gap junctions enable stem cells to overcome stromal inhibition? Leukemia, 11(8), 1281–1289.PubMedGoogle Scholar
  101. 101.
    Ruch, R. J., & Trosko, J. E. (2001). Gap-junction communication in chemical carcinogenesis. Drug Metabolism Reviews, 33(1), 117–124.PubMedGoogle Scholar
  102. 102.
    Russo, R. E., Reali, C., et al. (2008). Connexin 43 delimits functional domains of neurogenic precursors in the spinal cord. Journal of Neuroscience, 28(13), 3298–3309.PubMedGoogle Scholar
  103. 103.
    Saez, J. C., Berthoud, V. M., et al. (2003). Plasma membrane channels formed by connexins: Their regulation and functions. Physiological Reviews, 83(4), 1359–1400.PubMedGoogle Scholar
  104. 104.
    Sosinsky, G. E., & Nicholson, B. J. (2005). Structural organization of gap junction channels. Biochimica et Biophysica Acta, 1711(2), 99–125.PubMedGoogle Scholar
  105. 105.
    Sperger, J. M., Chen, X., et al. (2003). Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proceedings of National Academy of Sciences of the United State of America, 100(23), 13350–13355.Google Scholar
  106. 106.
    Stein, L. S., Boonstra, J., et al. (1992). Reduced cell–cell communication between mitotic and nonmitotic coupled cells. Experimental Cell Research, 198(1), 1–7.PubMedGoogle Scholar
  107. 107.
    Stojkovic, M., Lako, M., et al. (2004). Derivation of human embryonic stem cells from day-8 blastocysts recovered after three-step in vitro culture. Stem Cells, 22(5), 790–797.PubMedGoogle Scholar
  108. 108.
    Strelchenko, N., Verlinsky, O., et al. (2004). Morula-derived human embryonic stem cells. Reproductive Biomedicine Online, 9(6), 623–629.PubMedCrossRefGoogle Scholar
  109. 109.
    Tai, M. H., Olson, L. K., et al. (2003). Characterization of gap junctional intercellular communication in immortalized human pancreatic ductal epithelial cells with stem cell characteristics. Pancreas, 26(1), e18–e26.PubMedGoogle Scholar
  110. 110.
    Temme, A., Buchmann, A., et al. (1997). High incidence of spontaneous and chemically induced liver tumors in mice deficient for connexin32. Current Biology, 7(9), 713–716.PubMedGoogle Scholar
  111. 111.
    Thomson, J. A., Itskovitz-Eldor, J., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.PubMedGoogle Scholar
  112. 112.
    Todorova, M. G., Soria, B., et al. (2008). Gap junctional intercellular communication is required to maintain embryonic stem cells in a non-differentiated and proliferative state. Journal of Cellular Physiology, 214(2), 354–362.PubMedGoogle Scholar
  113. 113.
    Traver, D. a. & Akashi, K. (2004). Common myeloid progenitors. In Handbook of Stem Cells (M. a. T. 2005), Elsevier 1.Google Scholar
  114. 114.
    Trosko, J. E. (2003). Human stem cells as targets for the aging and diseases of aging processes. Medical Hypotheses, 60(3), 439–447.PubMedGoogle Scholar
  115. 115.
    Valiunas, V., Bukauskas, F. F., et al. (1997). Conductances and selective permeability of connexin43 gap junction channels examined in neonatal rat heart cells. Circulation Research, 80(5), 708–719.PubMedGoogle Scholar
  116. 116.
    Valiunas, V., Doronin, S., et al. (2004). Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. Journal of Physiology, 555(Pt 3), 617–626.PubMedGoogle Scholar
  117. 117.
    Valiunas, V., Polosina, Y. Y., et al. (2005). Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions. Journal of Physiology, 568(Pt 2), 459–468.PubMedGoogle Scholar
  118. 118.
    Vance, M. M., & Wiley, L. M. (1999). Gap junction intercellular communication mediates the competitive cell proliferation disadvantage of irradiated mouse preimplantation embryos in aggregation chimeras. Radiation Research, 152(5), 544–551.PubMedGoogle Scholar
  119. 119.
    Verfaillie, C. M., Pera, M. F., et al. (2002). Stem cells: hype and reality. Hematology (American Society of Hematology. Education Program), 369–391.Google Scholar
  120. 120.
    Villars, F., Guillotin, B., et al. (2002). Effect of HUVEC on human osteoprogenitor cell differentiation needs heterotypic gap junction communication. American Journal of Physiology. Cell Physiology, 282(4), C775–C785.PubMedGoogle Scholar
  121. 121.
    Vine, A. L., & Bertram, J. S. (2002). Cancer chemoprevention by connexins. Cancer Metastasis Reviews, 21(3–4), 199–216.PubMedGoogle Scholar
  122. 122.
    Wei, C. J., Xu, X., et al. (2004). Connexins and cell signaling in development and disease. Annual Review of Cell and Developmental Biology, 20, 811–838.PubMedGoogle Scholar
  123. 123.
    Weiss, M. L., & Troyer, D. L. (2006). Stem cells in the umbilical cord. Stem Cell Reviews, 2(2), 155–162.PubMedCrossRefGoogle Scholar
  124. 124.
    Wen, C. M., Cheng, Y. H., et al. (2008). Isolation and characterization of a neural progenitor cell line from tilapia brain. Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology, 149(2), 167–180.Google Scholar
  125. 125.
    Willecke, K., Eiberger, J., et al. (2002). Structural and functional diversity of connexin genes in the mouse and human genome. Biological Chemistry, 383(5), 725–737.PubMedGoogle Scholar
  126. 126.
    Wolvetang, E. J., Pera, M. F., et al. (2007). Gap junction mediated transport of shRNA between human embryonic stem cells. Biochemical and Biophysical Research Communications, 363(3), 610–615.PubMedGoogle Scholar
  127. 127.
    Wong, R. C., Dottori, M., et al. (2006). Gap junctions modulate apoptosis and colony growth of human embryonic stem cells maintained in a serum-free system. Biochemical and Biophysical Research Communications, 344(1), 181–188.PubMedGoogle Scholar
  128. 128.
    Wong, R. C., Pebay, A., et al. (2004). Presence of functional gap junctions in human embryonic stem cells. Stem Cells, 22(6), 883–889.PubMedGoogle Scholar
  129. 129.
    Worsdorfer, P., Maxeiner, S., et al. (2008). Connexin expression and functional analysis of gap junctional communication in mouse embryonic stem cells. Stem Cells, 26(2), 431–439.PubMedGoogle Scholar
  130. 130.
    Yamasaki, H., Krutovskikh, V., et al. (1999). Role of connexin (gap junction) genes in cell growth control and carcinogenesis. Comptes Rendus de l’AcadeÂmie des Sciences III, 322(2–3), 151–159.Google Scholar
  131. 131.
    Yang, S. R., Cho, S. D., et al. (2005). Role of gap junctional intercellular communication (GJIC) through p38 and ERK1/2 pathway in the differentiation of rat neuronal stem cells. Journal of Veterinary Medical Science, 67(3), 291–294.PubMedGoogle Scholar
  132. 132.
    Zhang, B., Pan, X., et al. (2006). MicroRNA: a new player in stem cells. Journal of Cellular Physiology, 209(2), 266–269.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Raymond C. B. Wong
    • 1
  • Martin F. Pera
    • 2
  • Alice Pébay
    • 3
  1. 1.Department of Biological ChemistryUniversity of California IrvineIrvineUSA
  2. 2.Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Centre for Neuroscience and Department of PharmacologyThe University of MelbourneParkvilleAustralia

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