Skip to main content
SpringerLink
Log in

Epigenetic programming of mesenchymal stem cells from human adipose tissue

  • Published:
Stem Cell Reviews Aims and scope Submit manuscript

Abstract

Stromal stem cells identified in various adult mesenchymal tissues (commonly called mesenchymal stem cells [MSCs]) have in past years received more attention as a result of their potential interest as replacement cells in regenerative medicine. An abundant and easily accessible source of adult human MSCs are stem cells harvested from liposuction material. Similarly to bone marrow-derived MSCs, human adipose tissue-derived stem cells (ASCs) can give rise to a variety of cell types in vitro and in vivo; however, they have a propensity to differentiate into primarily mesodermal lineages. Even so, their capacity to differentiate into nonadipogenic mesodermal pathways seems to be restricted. Emerging DNA methylation profiles at adipogenic and nonadipogenic gene promoters in freshly isolated, cultured, or differentiated ASCs aim to provide an epigenetic explanation for this restrictive differentiation potential. A review of these studies indicates that human ASCs are epigenetically marked by mosaic hypomethylation of adipogenic promoters, whereas nonadipogenic lineage-specific promoters are hypermethylated. Surprisingly, in vitro differentiation toward various pathways maintains the overall methylation profiles of undifferentiated cells, raising the hypothesis that ASCs are at least epigenetically preprogrammed for adipogenesis. Novel attempts at reprogramming the epigenome of MSCs have been initiated to enhance the differentiation capacity of these cells.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Verfaillie CM. Trends Cell Biol 2002;12:502–508.

    PubMed  CAS  Google Scholar 

  2. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Trends Biotechnol 2006;24:150–154.

    PubMed  CAS  Google Scholar 

  3. Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM. Exp Hematol 2002;30:896–904.

    PubMed  CAS  Google Scholar 

  4. Zuk PA, Zhu M, Mizuno H, et al. Tissue Eng 2001;7:211–228.

    PubMed  CAS  Google Scholar 

  5. Boquest AC, Shahdadfar A, Fronsdal K, et al. Mol Biol Cell 2005;16:1131–1141.

    PubMed  CAS  Google Scholar 

  6. Katz AJ, Tholpady A, Tholpady SS, Shang H, Ogle Rc. Stem Cells 2005;23:412–423.

    PubMed  CAS  Google Scholar 

  7. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Stem Cells 2006;24:1294–1301.

    PubMed  CAS  Google Scholar 

  8. Freitas CS, Dalmau SR. Cell Tissue Res 2006;325:403–411.

    PubMed  Google Scholar 

  9. Gronthos S, Zannettino AC, Hay SJ, et al. J Cell Sci 2003;116:1827–1835.

    PubMed  CAS  Google Scholar 

  10. Quirici N, Soligo D, Bossolasco P, Servida F, Lumini C, Deliliers GL. Exp Hematol 2002;30:783–791.

    PubMed  CAS  Google Scholar 

  11. Cowan CM, Shi YY, Aalami OO, et al. Nat Biotechnol 2004;22:560–567.

    PubMed  CAS  Google Scholar 

  12. Kang SK, Lee DH, Bae YC, Kim HK, Baik SY, Jung JS. Exp Neurol 2003;183:355–366.

    PubMed  CAS  Google Scholar 

  13. Cousin B, Andre M, Arnaud E, Penicaud L, Casteilla L. Biochem Biophys Res Commun 2003;301:1016–1022.

    PubMed  CAS  Google Scholar 

  14. Planat-Benard V, Silvestre JS, Cousin B, et al. Circulation 2004;109:656–663.

    PubMed  Google Scholar 

  15. Prunet-Marcassus B, Cousin B, Caton D, Andre M, Penicaud L, Casteilla L. Exp Cell Res 2006;312:727–736.

    PubMed  CAS  Google Scholar 

  16. Lachner M, Jenuwein T. Curr Opin Cell Biol 2002;14:286–298.

    PubMed  CAS  Google Scholar 

  17. Strahl BD, Allis CD. Nature 2000;403:41–45.

    PubMed  CAS  Google Scholar 

  18. Jenuwein T, Allis CD. Science 2001;293:1074–1080.

    PubMed  CAS  Google Scholar 

  19. Antequera F. Cell Mol Life Sci 2003;60:1647–1658.

    PubMed  CAS  Google Scholar 

  20. Li E, Bestor TH, Jaenisch R. Cell 1992;69:915–926.

    PubMed  CAS  Google Scholar 

  21. Li E, Beard C, Jaenisch R. Nature 1993;366:362–365.

    PubMed  CAS  Google Scholar 

  22. Panning B, Jaenisch R. Cell 1998;93:305–308.

    PubMed  CAS  Google Scholar 

  23. Brero A, Easwaran HP, Nowak D, et al. J Cell Biol 2005;169:733–743.

    PubMed  CAS  Google Scholar 

  24. Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR. J Biol Chem 2005;280:6257–6260.

    PubMed  CAS  Google Scholar 

  25. Rodic N, Oka M, Hamazaki T, et al. Stem cells 2005;23:1314–1323.

    PubMed  CAS  Google Scholar 

  26. Kubicek S, Schotta G, Lachner M, et al. Ernst Schering Res Found Workshop 2006;57:1–27.

    PubMed  CAS  Google Scholar 

  27. Szutorisz H, Dillon N. Bio Essays 2005;27:1286–1293.

    CAS  Google Scholar 

  28. Feldman N, Gerson A, Fang J, et al. Nat Cell Biol 2006;8:188–194.

    PubMed  CAS  Google Scholar 

  29. Strunnikova M, Schagdarsurengin U, Kehlen A, Garbe JC, Stampfer MR, Dammann R. Mol Cell Biol 2005:25:3923–3933.

    PubMed  CAS  Google Scholar 

  30. Laird PW. Hum Mol Genet 2005;14:R65-R76.

    PubMed  CAS  Google Scholar 

  31. Azuara V, Perry P, Sauer S, et al. Nat Cell Biol 2006;8:532–538.

    PubMed  CAS  Google Scholar 

  32. O'Neill LP, Vermilyea MD, Turner BM. Nat Genet 2006;38:835–841.

    PubMed  Google Scholar 

  33. Noer A, Sørensen AL, Boquest AC, Collas P. Mol Biol Cell 2006;17:3543–3556.

    PubMed  CAS  Google Scholar 

  34. Yatabe Y, Tavare S, Shibata D. Proc Natl Acad Sci USA 2001;98:10,839–10,844.

    CAS  Google Scholar 

  35. Kim JY, Siegmund KD, Tavare S, Shibata D. BMC Med 2005;3:10–16.

    PubMed  Google Scholar 

  36. Pfeifer GP, Steigerwald SD, Hansen RS, Gartler SM, Riggs AD. Proc Natl Acad Sci USA 1990;87:8252–8256.

    PubMed  CAS  Google Scholar 

  37. Silva AJ, Ward K, White R. Dev Biol 1993;156:391–398.

    PubMed  CAS  Google Scholar 

  38. Jones PA, Takai D. Science 2001;293:1068–1070.

    PubMed  CAS  Google Scholar 

  39. Zheng QH, Ma LW, Zhu WG, Zhang ZY, Tong TJ. J Cell Biochem 2006;98:1248.

    Google Scholar 

  40. Giebel B, Zhang T, Beckmann J, et al. Blood 2006;107:2146–2152.

    PubMed  CAS  Google Scholar 

  41. Clevers H. Nat Genet 2005;37:1027–1028.

    PubMed  CAS  Google Scholar 

  42. Zhu X, Deng C, Kuick R, et al. Proc Natl Acad Sci USA 1999;96:8058–8063.

    PubMed  CAS  Google Scholar 

  43. Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG. J Biol Chem 2000;275:2727–2732.

    PubMed  CAS  Google Scholar 

  44. Jones PA, Takai D. Science 2001;293:1068–1070.

    PubMed  CAS  Google Scholar 

  45. Kaneko KJ, Rein T, Guo SZ, Latham K, Depamphilis ML. Mol Cell Biol 2004;24:1968–1982.

    PubMed  CAS  Google Scholar 

  46. Melzner I, Scott V, Dorsch K, et al. J Biol Chem 2002;277:45,420–45,427.

    CAS  Google Scholar 

  47. Yokomori N, Tawata M, Onaya T. Diabetologia 2002;45:140–148.

    PubMed  CAS  Google Scholar 

  48. Heil M, Ziegelhoeffer T, Mees B, Schaper W. Circ Res 2004;94:573–574.

    PubMed  CAS  Google Scholar 

  49. Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A. Circulation 2004;110:349–355.

    PubMed  CAS  Google Scholar 

  50. Miyahara Y, Nagaya N, Kataoka M, et al. Nat Med 2006;12:459–465.

    PubMed  CAS  Google Scholar 

  51. Rehman J, Traktuev D, Li J, et al. Circulation 2004;109:1292–1298.

    PubMed  Google Scholar 

  52. Negrin RS, Contag CH. Nat Rev Immunol 2006;6:484–490.

    PubMed  CAS  Google Scholar 

  53. Ntziachristos V, Ripoll J, Wang LV, Weissleder R. Nat Biotechnol 2005;23:313–320.

    PubMed  CAS  Google Scholar 

  54. Welsh DK, Kay SA. Curr Opin Biotechnol 2005;16:73–78.

    PubMed  CAS  Google Scholar 

  55. Buck MJ, Lieb JD. Genomics 2004;83:349–360.

    PubMed  CAS  Google Scholar 

  56. Wilson IM, Davies JJ, Weber M. Cell Cycle 2006;5:155–158.

    PubMed  CAS  Google Scholar 

  57. Ballas N, Grunseich C, Lu DD, Speh JC, Mandel G. Cell 2005;121:645–657

    PubMed  CAS  Google Scholar 

  58. Montgomery ND, Yee D, Chen A, et al. Curr Biol 2005;15:942–947.

    PubMed  CAS  Google Scholar 

  59. Ringrose L, Ehret H, Paro R. Mol Cell 2004;16:641–653.

    PubMed  CAS  Google Scholar 

  60. Ayyanathan K, Lechner MS, Bell P, et al. Genes Dev 2003;17:1855–1869.

    PubMed  CAS  Google Scholar 

  61. Lehnertz B, Ueda Y, Derijck AA, et al. Curr Biol 2003;13:1192–1200.

    PubMed  CAS  Google Scholar 

  62. Fujita N, Watanabe S, Ichimura T, et al. J Biol Chem 2003;278:24,132–24,138.

    CAS  Google Scholar 

  63. Hochedlinger K, Jaenisch R. Nature 2006;441:1061–1067.

    PubMed  CAS  Google Scholar 

  64. Polyak K, Hahn WC. Nat Med 2006;12:296–300.

    PubMed  CAS  Google Scholar 

  65. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Nature 2002;418:41–49.

    PubMed  CAS  Google Scholar 

  66. Blelloch R, Wang, Z, Meissner A, Pollard S, Smith A, Jaenisch R. Stem Cells 2006;24:2007–2013.

    PubMed  CAS  Google Scholar 

  67. Yoo CB, Jones PA. Nat Rev Drug Discovery 2006;5:37–50.

    CAS  Google Scholar 

  68. Fuks F. Curr Opin Genet Dev 2005;15:490–495.

    PubMed  CAS  Google Scholar 

  69. Siegfried Z, Eden S, Mendelsohn M, Feng X, Tsuberi BZ, Cedar H. Nat Genet 1999;22:203–206.

    PubMed  CAS  Google Scholar 

  70. Stoner GD, Shimkin MB, Kniazeff AJ, Weisburger JH, Weisburger EK, Gori GB. Cancer Res 1973;33:3069–3085.

    PubMed  CAS  Google Scholar 

  71. Carr BI, Reilly JG, Smith SS, Winberg C, Riggs A. Carcinogenesis 1984;5:1583–1590.

    PubMed  CAS  Google Scholar 

  72. Mikol YB, Hoover KL, Creasia D, Poirier LA. Carcinogenesis 1983;4:1619–1629.

    PubMed  CAS  Google Scholar 

  73. Gaudet F, Hodgson JG, Eden A, et al. Science 2003;300:489–492.

    PubMed  CAS  Google Scholar 

  74. Holm TM, Jackson-Grusby L, Brambrink T, Yamada Y, Rideout WM III, Jaenisch R. Cancer Cell 2005;8:275–285.

    PubMed  CAS  Google Scholar 

  75. Hou M, Wang X, Popov N, et al. Exp Cell Res 2002;274:25–34.

    PubMed  CAS  Google Scholar 

  76. Mukhopadhyay NK, Gordon GJ, Maulik G, et al. J Cell Mol Med 2005;9:662–669.

    PubMed  CAS  Google Scholar 

  77. Hattori N, Nishino K, Ko YG, et al. J Biol Chem 2004;279:17,063–17,069.

    CAS  Google Scholar 

  78. Mohana KB, Jin HF, Kim JG, et al. Cell Tissue Res 2006;325:445–454.

    Google Scholar 

  79. Enright BP, Kubota C, Yang X, Tian XC. Biol Reprod 2003;69:896–901.

    PubMed  CAS  Google Scholar 

  80. Enright BP, Sung LY, Chang CC, Yang X, Tian XC. Biol Reprod 2005;72:944–948.

    PubMed  CAS  Google Scholar 

  81. Kishigami S, Mizutani E, Ohta H, et al. Biochem Biophys Res Commun 2006;340:183–189.

    Article  PubMed  CAS  Google Scholar 

  82. Rybouchkin A, Kato Y, Tsunoda Y. Biol Reprod 2006;74:1083–1089.

    PubMed  CAS  Google Scholar 

  83. Cho HH, Park HT, Kim YJ, Bae YC, Suh KT, Jung JS. J Cell Biochem 2005;96:533–542.

    PubMed  CAS  Google Scholar 

  84. Makino S, Fukuda K, Miyoshi S, et al. J Clin Invest 1999;103:697–705.

    Article  PubMed  CAS  Google Scholar 

  85. Rangappa S, Fen C, Lee EH, Bongso A, Wei ES. Ann Thorac Surg 2003;75:775–779.

    PubMed  Google Scholar 

  86. Milhem M, Mahmud N, Lavelle D, et al. Blood 2004;103:4102–4110.

    PubMed  CAS  Google Scholar 

  87. Araki H, Mahmud N, Milhem M, et al. Exp Hematol 2006;34:140–149.

    PubMed  CAS  Google Scholar 

  88. Araki H, Mahmud N, Milhem M, et al. Exp Hematol 2006;34:140–149.

    PubMed  CAS  Google Scholar 

  89. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB. Nat Genet 1999;21:103–107.

    PubMed  CAS  Google Scholar 

  90. Lassar AB, Paterson BM, Weintraub H. Cell 1986;47:649–656.

    PubMed  CAS  Google Scholar 

  91. Schmittwolf C, Kirchhof N, Jauch A, et al. EMBO J 2005;24:554–566.

    PubMed  CAS  Google Scholar 

  92. Sigurjonsson OE, Perreault MC, Egeland T, Glover JC. Proc Natl Acad Sci USA 2005;102:5227–5232.

    PubMed  CAS  Google Scholar 

  93. Cai J, Cheng A, Luo Y, et al. J Neurochem 2004;88:212–226.

    Article  PubMed  CAS  Google Scholar 

  94. Chute JP, Muramoto GG, Whitesides J, et al. Proc Natl Acad Sci USA 2006;103:11,707–11,712.

    CAS  Google Scholar 

  95. Corti S, Locatelli F, Papadimitriou D, et al. Stem Cells 2006;24:975–985.

    PubMed  CAS  Google Scholar 

  96. Boyer LA, Plath K, Zeitlinger J, et al. Nature 2006;441:349–353.

    PubMed  CAS  Google Scholar 

  97. Lee TI, Jenner RG, Boyer LA, et al. Cell 2006;125:301–313.

    PubMed  CAS  Google Scholar 

  98. Loh YH, Wu Q, Chew JL, et al. Nat Genet 2006;38:431–440.

    PubMed  CAS  Google Scholar 

  99. Weber M, Davies JJ, Wittig D, et al. Nat Genet 2005;37:853–862.

    PubMed  CAS  Google Scholar 

  100. Bernstein BE, Mikkelsen TS, Xie X, et al. Cell 2006;125:315–326.

    PubMed  CAS  Google Scholar 

  101. Rideout WM III, Wakayama T, Wutz A, et al. Nat Genet 2000;24:109–110.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, Blindern, PO Box 1112, 0317, Oslo, Norway

    Andrew C. Boquest, Agate Noer & Philippe Collas

Authors
  1. Andrew C. Boquest
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agate Noer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philippe Collas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philippe Collas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boquest, A.C., Noer, A. & Collas, P. Epigenetic programming of mesenchymal stem cells from human adipose tissue. Stem Cell Rev 2, 319–329 (2006). https://doi.org/10.1007/BF02698059

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02698059

Index Entries

Search

Navigation