Reversible epithelio-mesenchymal transformations of cells in embryogenesis and postnatal tissue regeneration

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Abstract

The modern findings on gene expression interchanging that characterize manifestation of epithelial and mesodermal (mesenchymal) cells within early embryogenesis are presented. Based on our data obtained while using immunocytochemisrty method (CD43, CD45, CD14, CD44, CD54, CD56, CD90, CD105 antibodies) the authors consider the part of mesenchymal stem cells to be epithelial ones. It is suggested that interchanging of epithelial and mesenchymal phenotype features are general biologic natural phenomenon in ontogenesis.

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V. S. Repin

A.Ya. Friedenshtein Research Institute of cellular technologies and regenerative medicine

Author for correspondence.
Email: redaktor@celltranspl.ru
Russian Federation, Moscow

I. N. Saburina

A.Ya. Friedenshtein Research Institute of cellular technologies and regenerative medicine

Email: redaktor@celltranspl.ru
Russian Federation, Moscow

References

  1. Kadokawa Y., Fuketa I., Nose A. et al. Expression pattern of E- and P-cadherin in mouse embryos and uteri during the preimplantation period. Develop. Growth Differ. 1989; 31: 23-30.
  2. Thiery J.P. Epithelio-mesenchymal transformation and cancer. Nat. Rev. Cancer. 2002; 2: 442-54.
  3. . Thiery J.P. Epithelio-mesenchymal transitions in development and pathologies. Curr. Opin. Cell Biol. 2003; 15: 740-46.
  4. Thiery J.P., Sleeman J.P. Complex networks orchestrate epithelial- mesenchymal transitions. Nat. Rev. Mol. Cell Biol. 2006; 7: 131 -41.
  5. Li L., Arman E., Ekholm P. et al. Distinct GATA6- and laminin-dependent mechanisms regulate endodermal and ectodermal ESC fates. Development. 2004; 131: 5277-86.
  6. Braga V.M., Machesky L.M., Hall A. et al. The small GTP-ase Rho A and Rac1 are required for the establishment of cadherin-dependent cell-cell contacts. J. Cell Biol. 1997; 137:1421-31.
  7. Kim K., Lu Z., Hay E.D. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biol. Int. 2002; 26: 463-76.
  8. Chen, Y., Li X., Eswarakumar V.P. et al. FGF signaling through PI 3-kinase and Akt/PkB is required for embryoid body differentiation. Oncogene. 2000; 19: 3750-56.
  9. Kemler R., Hierholzer A., Kanzler B. et al. Stabilization of beta-catenin in the mouse zygote leads to premature epithelial-mesenchymal transition in the epiblast. Development 2004; 131: 5817-24.
  10. Kim K., Lu Z., Hay E.D. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biol. Int. 2002; 26: 463-76.
  11. Artas A.M. Еpithelial - mesenchymal interactions in cancer and development. Cell 2001; 105: 425-31.
  12. Ciruna B., Rossant J. FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev. Cell. 2001; 1: 37-49.
  13. DeCraene B., van Roy F., Berx G. Unraveling signaling cascade from the Snail family of transcription factors. Cell Signalling 2005; 17: 535-47.
  14. Hemavathy K., Ashraf S.I., Ip Y.T. Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene 2000; 257: 1-12.
  15. Yang X., Li C., Xu X. et al. Tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. Proc. Natl. Acad. Sci. USA 1998. 95. 3667 - 72
  16. Fehling H.J., Lacaud G., Kubo A. et al. Tracking mesoderm induction and its specialization to the hemangioblasts during ESC differentiation. Differentiation. 2003; 130: 4217-27.
  17. Gadue P., Huber T.L., Nostro C. et al. Germ layer induction from ESC. Exp. Hematol. 2005; 33: 955-64.
  18. Bertochini F., Skromne I., Wolpert L. et al. Determination of embryonic polarity in a regulative system: evidence for endogenous inhibitors acting sequentially during primitive streak formation in the chick embryo. Development 2004; 131: 3381-90.
  19. Arnold S.J., Stappert J., Bauer A. et al. Brachyury is a target gene of the Wnt/beta-catenin signaling pathway. Mech. Dev. 2000; 91: 249-58.
  20. Yamaguchi T.P., Takada S., Yoshikawa Y. e al. Brachyury is a direct target of Wnt3a during paraxial mesoderm specification. Genes. Dev. 1999; 13: 3185-90.
  21. Galceran J., Hsu S.C., Grosschedl R. Rescue of a Wnt 3a mutation by an activated form of LEF-1: regulation of maintenance but not initiation of Brachyury expression. Proc. Natl. Acad. Sci. USA 2001 ; 98: 8668-73.
  22. Beck S., Le Good A., Guzman M. et al. Еxtraembryonic proteases regulate Nodal signaling during gastrulation. Nat. Cell Biol. 2002; 4: 981-87.
  23. Koblar S.A., Murphy M., Barrett G.L. et al. Pax-3 regulates neurogenesis in neural crest-derived precursor cells J. Neurosci. Res. 1999; 56: 518-30.
  24. Van Aelst L., Symons M. Role of Rho family of GTP-ases in epithelial morphogenesis. Genes. Dev. 2002; 16: 1032-54.
  25. Schratt G., Philippar U., Berger J. et al. Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in ESC. J. Cell Biol. 2002; 156: 737-50.
  26. Palacious F., Tushir J.S., Fujita Y. et al. Lysosomal targeting of E-cadherin: a unique mechanism for down-regulation of cell-cell adhesion during epithelial- to-mesenchymal transition. Mol. Cell Biol. 2005; 25: 389-99.
  27. Pourquie O. Vertebrate somitogenesis. Ann. Rev. Cell Dev. Biol. 2001; 17: 311-50.
  28. Houselstein D., Auda-Boucher G., Cheraud V. et al. Hox-gene Msx1 is expressed in a subset of somites and in muscle progenitor cells migrating into limbs. Development 1999; 126: 2689-701.
  29. Burdsal C.A., Damsky C.H., Pedersen R.A. The role of E-cadherin and integrins in mesoderm differentiation and migration at the mammalian primitive streak. Development 1993; 118: 829-44.
  30. Prusa A.R., Marton E., Rosner M. et al. Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research? Hum. Reprod. 2003; 18: 1489-93.
  31. Miki T., Lehmann T., Cai H. et al. Stem cell characteristics of amniotic epithelial cells. Stem Cells 2005; 23: 1549-59.
  32. Behr R., Heneweer C., Viebahn C. et al. Epithelial-mesenchymal transitions in colonies of rhesus monkey ESC: a model for processes involved in gastrulation. Stem Cells 2005; 23: 805-16.
  33. Green J.B., Dominiguez I., Davidson L.A. Self-organization of vertebrate mesoderm based on simple boundary conditions. Dev. Dyn. 2004; 231: 576-81.
  34. James R.G., Schulteiss T.M. BMP signaling promotes intermediate mesoderm gene expression in a dose-dependent, cell-autonomous and translation-dependent manner. Dev. Biol. 2005; 288: 113-25.
  35. Tada S., Era T., Furusawa C. et al. Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in ESC culture. Development 2005; 132: 4363-74.
  36. Belaoussoff M., Farrington S.M., Baron M.H. Hemopoietic induction and re-specification of A-P identity by visceral endoderm signaling in the mouse embryo. Development 1998; 125: 5009-18.
  37. Huber T.L., Kouskoff V., Fehling H.J. et al. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 2004; 432: 625-30.
  38. Rossant E.M. Cell fate decisions in early blood vessel formation. Trends Cardiovasc. Med. 2003; 13: 254-59.
  39. Sakurai H., Era T., Jakt L.M. et al. In vitro modeling of paraxial and lateral mesoderm differentiation reveals early reversibility. Stem Cells 2006; 24: 575-86.
  40. Hay E.D. An overview of epithelio-mesenchymal transformation. Acta Anat. 1995; 154: 8-20.
  41. Hay E.D. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev. Dyn. 2005; 233: 706-20.
  42. Hay E.D., Zuk A. Transformation between epithelium and mesenchyme: normal, pathological and experimentally induced. Am. J. Kidney Dis. 1995; 26: 678-90.
  43. Shook D., Keller R. Mechanism, mechanics and function of epithelial- mesenchymal transition in the early development. Mech. Dev. 2003; 120: 13511383.
  44. Nakaya Y., Kuroda S., Kataquri Y.T. et al. Mesenchymal-epithelial transition during somatic segmentation is regulated by differential roles of Cdc42 and Rac1. Dev. Cell. 2004; 7: 425-38.
  45. Meriane M., Charrasse S., Comunale F. et al. Participation of small GTF-ase Rac1 and Cdc42Hs in myoblast transformation. Oncogene 2002; 21: 2901-07.
  46. Eloy-Trinquet S., Nicolas J.F. Cell coherence during production of presomitic mesoderm and somitogenesis in the mouse embryo. Development 2002; 129: 3609-19.
  47. Репин В.С. Стволовые клетки сердечно-сосудистой системы и атеросклероз. Патогенез 2004; 1: 9-20.
  48. Tevosian S.G., Deconinck A.E., Tanaka M. et al. FOG-2 is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell 2000; 101: 729-39.
  49. Wada A.M., Willet S.D., Bader D.M. et al. Coronary vessel development. Arterioscl. Thromb. Vasc. Biol. 2003; 23: 2138-45.
  50. Reese D.E., Mikawa T., Bader D.M. et al. Development of the coronary vessel system. Circ. Res. 2002; 91: 751-68.
  51. Dorsky R.I., Moon R.T., Raible D.W. Control of neural crest cell fate by the Wnt signaling pathway. Nature 1998; 396: 370-75.
  52. Dorsky R.I., Moon R.T., Raible D.W. Environmental signals and cell fate specification in premigratory neural crest. Bioessays 2000; 22: 708-16.
  53. LaBonne C., Bonner-Fraser M. Molecular mechanism of neural crest formation. Ann. Rev. Cell Biol. 1999; 15: 81-112.
  54. Weston J.A., Yoshida H., Robinson V. et al. Neural crest and the origin of the ectomesenchyme: neural fold heterogeneity suggests an alternative hypothesis. Dev. Dyn. 2004; 229: 118-30.
  55. Cheung M., Chaboissier M.C., Mynett A. et al. The transcriptional control of trunk neural crest induction, survival and delamination. Development 2005; 8: 179-92.
  56. Trainor P., Krumlauf R. Riding the crest of the Wnt signaling wave. Science 2002; 292: 781-84.
  57. Takahashi K., Nuckolls G.H., Takahashi Y. et al. Msx2 is a repressor of chondrogenic differentiation in migratory cranial neural crest. Dev. Dyn. 2001 ; 222: 252-62.
  58. Xu H., Firulli A.B., Zhang X. et al. HAND2 synergistically enhances transcription of dopamine-B-hydroxylase in the presense of Phox2a. Dev. Biol. 2003; 114: 66-77.
  59. Dupin E., Glavieux C., Vaigot P. et al. Endothelin 3 induce the reversion of melanocytes to glia through neural crest derived glial-melanocyte progenitor. Proc. Natl. Acad. Sci. USA 2000; 97: 7882-87.
  60. Dunn K.J., Wlliams B.O., Pavan W.J. Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development. Proc. Natl. Acad. Sci. USA 2000; 97: 10050-55.
  61. Репин B.0., 0ухих Г.Т. Медицинская клеточная биология. 1998. Из-во БЭБМ: РАМН, Москва.
  62. Bilodeau M.L., Boulineau T., Hullinger R.L. et al. cAMP signaling functions as a bimodal switch in sympathoadrenal cell development in cultured primary neural crest cells. Mol. Cell. Biol. 2000; 20: 3004-14.
  63. Youn Y.H., Feng J., Tessarollo L. et al. Neural crest stem cells and cardiac endothelium defects in the Trk C null mutants. Mol. Cell. Neurosci. 2003; 124: 1333-9.
  64. Spees J.L., Olson S.D., Ylostalo J. et al. Differentiation, cell fusion and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc. Natl. Acad. Sci. USA 2003; 100: 2397-402.
  65. Prockop S.J., Gregory C.A., Spees J.L. One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc. Natl. Acad. Sci. USA 2003; 100: 11917-23.
  66. Wang G., Bunnell B., Painter R.G. et al. Potential of BM-MSC for cystic fibrosis therapy. Mol. Therapy 2004; 9: Suppl. 1: 195-205.
  67. Wang G., Bunnell B.A., Painter R.G. et al. Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc. Natl. Acad. Sci. USA 2005; 102: 188-91.
  68. Fritsch C., Swietlicki E.A., Lefebvre O. et al. Epimorphin expression in intestinal myofibroblasts induces epithelial morphogenesis. J. Clin. Invest. 2002; 110: 1629-41.
  69. Poulsom R., Forbes S.J., Hodivala-Dilke K. et al. Bone marrow contributes to renal parenchymal turnover and regeneration. J. Pathol. 2003; 195: 229-35.
  70. Luk J.M., Wang P.P., Lee C.K. et al. Hepatic potential of bone marrow stromal cells: development of in vitro co-culture and intra-portal transplantation models. J. Immunol. Methods 2005; 305: 39-47.
  71. Okumoto K., Saito T., Hattori E. et al. Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation. Biochem. Biophys. Res. Comms. 2003; 304: 691 -95.
  72. Inderbitzin M.D., Avital I., Keogh A. et al. Interleukin3 induces hepatocytespecific metabolic activity in bone marrow-derived liver stem cells. J. Gastrointest. Surg. 2005. 9. 69 - 73. Kang Y., Massague J. Epithelio-mesenchymal transitions: Twist in development and metastasis. Cell 2004; 118: 277-79.
  73. Seshi B., Kumar S., King D. et al. Multilineage gene expression in human bone marrow stromal cells as evidenced by single-cell microarray analysis. Blood Cells Mol. Dis. 2003; 31: 268-85.
  74. DiGirolamo C.M., Stokes D., Colter D. et al. Propagation and senescence of human bone marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br. J. Hematol. 1999; 107: 275-81.
  75. Baddoo M., Hill K., Wilkinson R. et al. Characterization of MSC isolated from murine bone marrow by negative selection. J. Cell Biochem. 2003; 89: 1235-49.

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig.1. Morphology of human bone marrow cell culture (lens S20 ): A – epithelioid colony; B – fibroblast - like Bacolod

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3. Fig. 2. Immunohistochemical analysis of epithelioid cell colonies from bone marrow:A - expression of nestin (lens x20); B - expression of E-cadherin (lens x20); C - co-expression of nestin and vimentin (lens x10); D- expression of a-actin MMC (lens x40)Pre-painting of cores - Hoechst

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4. Fig. 2_2

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5. Fig. 2_3

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6. Fig. 3. Immunohistochemical analysis of fibroblast–like cell colonies from bone marrow: A - expression of E-cadherin (lens x20); B - expression of nestin (lens x20); C - expression of α-actin MMC (lens x40) Pre–coloring of nuclei - Hoechst

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7. Fig. 4. Expression in MSCS culture isolated from bone marrow: von Willebrand A-factor (VWF); B – CD105 (х40 lens) Pre–painting of cores - Hoechst

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8. Figure 5. Immunohistochemical analysis of postnatal progenitor cells from human adipose tissue:A - expression of E-cadherin (lens x30); B — co—expression of nestin and vimentin (lens x10); C - expression of a-actin MMC (lens x40)Pre—painting of cores - Hoechst

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9. Fig.5_2

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10. Fig.5_3

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