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Delaney SP, Julian LM, Stanford WL. The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis. Front Cell Dev Biol. 2014;2:69doi: 10.3389/fcell.2014.00069.
Delaney, S. P., Julian, L. M., & Stanford, W. L. (2014). The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis. Frontiers in cell and developmental biology, 269. https://doi.org/10.3389/fcell.2014.00069
Delaney, Sean P, et al. "The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis." Frontiers in cell and developmental biology vol. 2 (2014): 69. doi: https://doi.org/10.3389/fcell.2014.00069
Delaney SP, Julian LM, Stanford WL. The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis. Front Cell Dev Biol. 2014 Nov 25;2:69. doi: 10.3389/fcell.2014.00069. eCollection 2014. PMID: 25505789; PMCID: PMC4243694.
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Front Cell Dev Biol. 2014 Nov 25;2:69. doi: 10.3389/fcell.2014.00069. eCollection 2014.

The neural crest lineage as a driver of disease heterogeneity in Tuberous Sclerosis Complex and Lymphangioleiomyomatosis.

Frontiers in cell and developmental biology

Sean P Delaney, Lisa M Julian, William L Stanford

Affiliations

  1. Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute Ottawa, ON, Canada ; Faculty of Graduate and Postdoctoral Studies, University of Ottawa Ottawa, ON, Canada ; Department of Cellular and Molecular Medicine, University of Ottawa Ottawa, ON, Canada.
  2. Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute Ottawa, ON, Canada ; Faculty of Graduate and Postdoctoral Studies, University of Ottawa Ottawa, ON, Canada.
  3. Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute Ottawa, ON, Canada ; Faculty of Graduate and Postdoctoral Studies, University of Ottawa Ottawa, ON, Canada ; Department of Cellular and Molecular Medicine, University of Ottawa Ottawa, ON, Canada ; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa Ottawa, ON, Canada.

PMID: 25505789 PMCID: PMC4243694 DOI: 10.3389/fcell.2014.00069

Abstract

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease, best characterized by the formation of proliferative nodules that express smooth muscle and melanocytic antigens within the lung parenchyma, leading to progressive destruction of lung tissue and function. The pathological basis of LAM is associated with Tuberous Sclerosis Complex (TSC), a multi-system disorder marked by low-grade tumors in the brain, kidneys, heart, eyes, lung and skin, arising from inherited or spontaneous germ-line mutations in either of the TSC1 or TSC2 genes. LAM can develop either in a patient with TSC (TSC-LAM) or spontaneously (S-LAM), and it is clear that the majority of LAM lesions of both forms are characterized by an inactivating mutation in either TSC1 or TSC2, as in TSC. Despite this genetic commonality, there is considerable heterogeneity in the tumor spectrum of TSC and LAM patients, the basis for which is currently unknown. There is extensive clinical evidence to suggest that the cell of origin for LAM, as well as many of the TSC-associated tumors, is a neural crest cell, a highly migratory cell type with extensive multi-lineage potential. Here we explore the hypothesis that the types of tumors that develop and the tissues that are affected in TSC and LAM are dictated by the developmental timing of TSC gene mutations, which determines the identities of the affected cell types and the size of downstream populations that acquire a mutation. We further discuss the evidence to support a neural crest origin for LAM and TSC tumors, and propose approaches for generating humanized models of TSC and LAM that will allow cell of origin theories to be experimentally tested. Identifying the cell of origin and developing appropriate humanized models is necessary to truly understand LAM and TSC pathology and to establish effective and long-lasting therapeutic approaches for these patients.

Keywords: Lymphangioleiomyomatosis; Tuberous Sclerosis; cell of origin; disease modeling; neural crest

References

  1. Acta Neuropathol. 1997 Aug;94(2):180-6 - PubMed
  2. Am J Hum Genet. 1999 Apr;64(4):986-92 - PubMed
  3. Handb Clin Neurol. 2013;111:323-31 - PubMed
  4. Hum Mol Genet. 2012 Oct 1;21(19):4286-300 - PubMed
  5. Nat Cell Biol. 2000 May;2(5):281-7 - PubMed
  6. Nat Cell Biol. 2004 Nov;6(11):1082-93 - PubMed
  7. PLoS One. 2009;4(2):e4381 - PubMed
  8. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14960-5 - PubMed
  9. Neurology. 2010 May 25;74(21):1716-23 - PubMed
  10. Am J Hum Genet. 2001 Jan;68(1):64-80 - PubMed
  11. Dev Biol. 2012 Apr 15;364(2):162-77 - PubMed
  12. Development. 2001 Apr;128(7):1059-68 - PubMed
  13. Cell. 1993 Dec 31;75(7):1305-15 - PubMed
  14. Ophthalmic Genet. 2010 Dec;31(4):209-14 - PubMed
  15. Lymphat Res Biol. 2010 Mar;8(1):43-9 - PubMed
  16. PLoS One. 2010 Nov 09;5(11):e13890 - PubMed
  17. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2635-40 - PubMed
  18. Hum Pathol. 2003 Jan;34(1):95-8 - PubMed
  19. Am J Surg Pathol. 2011 Dec;35(12):1776-85 - PubMed
  20. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19384-9 - PubMed
  21. Hum Mol Genet. 2011 Feb 1;20(3):445-54 - PubMed
  22. Dev Biol. 2007 Nov 1;311(1):159-71 - PubMed
  23. Hum Mol Genet. 2009 Jul 1;18(13):2378-87 - PubMed
  24. J Comp Neurol. 1954 Oct;101(2):515-41 - PubMed
  25. Hum Mol Genet. 2012 Feb 15;21(4):799-810 - PubMed
  26. Am J Hum Genet. 2001 Sep;69(3):493-503 - PubMed
  27. Cell Stem Cell. 2009 May 8;4(5):453-63 - PubMed
  28. Neurobiol Dis. 2012 Jan;45(1):369-80 - PubMed
  29. J Clin Invest. 2011 Apr;121(4):1596-607 - PubMed
  30. Hum Mutat. 1999;14(5):412-22 - PubMed
  31. Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12455-60 - PubMed
  32. Hum Genet. 2010 Mar;127(5):573-82 - PubMed
  33. Dermatology. 2014;228(1):37-41 - PubMed
  34. Nat Cell Biol. 2001 Sep;3(9):778-84 - PubMed
  35. Medicine (Baltimore). 1999 Sep;78(5):321-37 - PubMed
  36. Science. 1983 Jun 3;220(4601):1059-61 - PubMed
  37. Nat Med. 2008 Aug;14(8):843-8 - PubMed
  38. Am J Respir Cell Mol Biol. 2006 Apr;34(4):473-80 - PubMed
  39. Nature. 2014 Jun 19;510(7505):393-6 - PubMed
  40. J Histochem Cytochem. 2004 Dec;52(12):1537-42 - PubMed
  41. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6085-90 - PubMed
  42. Dev Med Child Neurol. 2014 Dec;56(12):1207-11 - PubMed
  43. Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17462-7 - PubMed
  44. Neurol Clin. 2003 Nov;21(4):983-1004 - PubMed
  45. N Engl J Med. 2006 Sep 28;355(13):1345-56 - PubMed
  46. Adv Exp Med Biol. 2006;589:170-80 - PubMed
  47. Pediatrics. 2011 May;127(5):e1335-7 - PubMed
  48. Br J Ophthalmol. 2006 Aug;90(8):1067-8 - PubMed
  49. Arch Dermatol. 2011 Sep;147(9):1116-7 - PubMed
  50. Genet Med. 2007 Feb;9(2):88-100 - PubMed
  51. Development. 2007 Jun;134(12):2283-92 - PubMed
  52. Am J Respir Crit Care Med. 2010 Aug 15;182(4):531-9 - PubMed
  53. Am J Pathol. 2013 Jul;183(1):226-34 - PubMed
  54. Neuron. 2013 Jun 5;78(5):895-909 - PubMed
  55. Am J Respir Cell Mol Biol. 2010 Feb;42(2):227-34 - PubMed
  56. J Cutan Pathol. 2001 Oct;28(9):470-5 - PubMed
  57. Cancer Res. 2004 Feb 1;64(3):812-6 - PubMed
  58. Am J Surg Pathol. 2004 Aug;28(8):1007-16 - PubMed
  59. Cell Mol Life Sci. 2013 Aug;70(16):2887-98 - PubMed
  60. Dev Biol. 1990 Oct;141(2):243-53 - PubMed
  61. Am J Pathol. 2009 Dec;175(6):2252-4 - PubMed
  62. Am J Hum Genet. 1999 Jun;64(6):1632-7 - PubMed
  63. Cell Adh Migr. 2008 Oct-Dec;2(4):223-30 - PubMed
  64. Acta Neuropathol. 1996;91(4):368-75 - PubMed
  65. Brain Pathol. 2010 Nov;20(6):1096-105 - PubMed
  66. Hum Mol Genet. 2014 Apr 15;23(8):2023-9 - PubMed
  67. Neurology. 2003 Aug 12;61(3):409-12 - PubMed
  68. J Am Acad Dermatol. 2002 Mar;46(3):376-80 - PubMed
  69. Virchows Arch. 2008 Feb;452(2):119-32 - PubMed
  70. Dev Dyn. 2012 Aug;241(8):1333-49 - PubMed
  71. J Med Genet. 1999 Apr;36(4):285-9 - PubMed
  72. Nat Cell Biol. 2000 Feb;2(2):76-83 - PubMed
  73. Hum Mol Genet. 2009 Apr 1;18(7):1252-65 - PubMed
  74. Development. 1996 Oct;122(10):3229-42 - PubMed
  75. Circ Res. 2013 Sep 27;113(8):e76-86 - PubMed
  76. J Med Genet. 2000 Jan;37(1):55-7 - PubMed
  77. Stem Cells. 2010 Nov;28(11):2027-40 - PubMed
  78. Virchows Arch. 2014 Apr;464(4):495-503 - PubMed
  79. PLoS One. 2013 May 16;8(5):e64224 - PubMed
  80. J Embryol Exp Morphol. 1973 Aug;30(1):31-48 - PubMed
  81. Oncogene. 2002 Jun 6;21(25):4050-9 - PubMed
  82. Am J Respir Crit Care Med. 2001 Jan;163(1):253-8 - PubMed
  83. J Med Genet. 1996 Nov;33(11):962-4 - PubMed
  84. Ann Neurol. 2006 Nov;60(5):528-39 - PubMed
  85. PLoS One. 2011;6(9):e23379 - PubMed
  86. Dev Biol. 2012 Jun 1;366(1):83-95 - PubMed
  87. Glia. 2011 May;59(5):771-84 - PubMed
  88. Cell. 1996 May 3;85(3):331-43 - PubMed
  89. Am J Pathol. 2010 Oct;177(4):1765-78 - PubMed
  90. Genes Dev. 2011 Aug 1;25(15):1595-600 - PubMed
  91. Clin Genet. 2014 Aug;86(2):149-54 - PubMed
  92. Dev Biol. 1983 Jun;97(2):433-43 - PubMed
  93. Eur Respir Rev. 2012 Sep 1;21(125):196-206 - PubMed
  94. Am J Respir Crit Care Med. 2003 Apr 1;167(7):976-82 - PubMed
  95. Dev Med Child Neurol. 1996 Feb;38(2):146-55 - PubMed
  96. Development. 2008 May;135(10):1771-80 - PubMed
  97. Chest. 1999 Apr;115(4):1041-52 - PubMed
  98. Pediatr Neurol. 2013 Oct;49(4):243-54 - PubMed
  99. N Engl J Med. 2010 Nov 4;363(19):1801-11 - PubMed
  100. Am J Hum Genet. 1998 Apr;62(4):810-5 - PubMed
  101. Am J Hum Genet. 1996 Aug;59(2):400-6 - PubMed
  102. Curr Opin Pediatr. 2006 Dec;18(6):634-8 - PubMed
  103. Cell. 2012 Apr 13;149(2):274-93 - PubMed
  104. Ann Neurol. 2006 Mar;59(3):490-8 - PubMed
  105. Cancer Res. 1999 Mar 15;59(6):1206-11 - PubMed
  106. J Med Genet. 2001 May;38(5):347-9 - PubMed
  107. PLoS One. 2013;8(3):e60014 - PubMed
  108. Dev Biol. 2012 Jun 1;366(1):34-54 - PubMed
  109. Hum Genet. 2000 Aug;107(2):97-114 - PubMed
  110. Am J Anat. 1983 Apr;166(4):445-68 - PubMed
  111. J Hum Genet. 2002;47(1):20-8 - PubMed
  112. Curr Opin Oncol. 2014 Mar;26(2):215-21 - PubMed
  113. Hum Mutat. 2011 May;32(5):557-63 - PubMed
  114. Development. 1995 Feb;121(2):525-38 - PubMed
  115. Arch Bronconeumol. 2011 Sep;47(9):470-2 - PubMed
  116. J Child Neurol. 2006 Mar;21(3):199-204 - PubMed
  117. Hum Pathol. 1997 Sep;28(9):1071-8 - PubMed
  118. Lymphat Res Biol. 2010 Mar;8(1):51-7 - PubMed
  119. Neurology. 2005 Apr 26;64(8):1446-9 - PubMed
  120. BMC Med Genet. 2008 Feb 26;9:10 - PubMed
  121. Nat Genet. 1994 Feb;6(2):193-6 - PubMed
  122. J Neurosci. 2007 May 23;27(21):5546-58 - PubMed
  123. Cancer Cell. 2012 Dec 11;22(6):725-36 - PubMed
  124. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):527-33 - PubMed
  125. Science. 2013 Aug 23;341(6148):860-3 - PubMed
  126. Kidney Int. 2004 Sep;66(3):924-34 - PubMed
  127. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8762-7 - PubMed
  128. J Child Neurol. 2004 Sep;19(9):716-25 - PubMed
  129. Genesis. 2013 Apr;51(4):284-92 - PubMed
  130. N Engl J Med. 2011 Apr 28;364(17):1595-606 - PubMed
  131. J Clin Invest. 2012 Nov;122(11):3807-16 - PubMed
  132. Eur J Hum Genet. 2005 Jan;13(1):59-68 - PubMed
  133. PLoS One. 2011;6(9):e24919 - PubMed
  134. Cell Rep. 2013 Oct 31;5(2):433-44 - PubMed
  135. Hum Mol Genet. 2002 Mar 1;11(5):525-34 - PubMed
  136. Cancer Cell. 2012 Dec 11;22(6):709-24 - PubMed
  137. Cell Stem Cell. 2009 Dec 4;5(6):610-23 - PubMed
  138. Childs Nerv Syst. 2014 Feb;30(2):227-40 - PubMed
  139. Int J Dev Biol. 2005;49(2-3):151-9 - PubMed
  140. Skeletal Radiol. 1997 Mar;26(3):184-7 - PubMed
  141. Stem Cells. 2005 Jun-Jul;23(6):727-37 - PubMed
  142. J Clin Invest. 1999 Sep;104(6):687-95 - PubMed
  143. Mayo Clin Proc. 2000 Jun;75(6):591-4 - PubMed
  144. Neurology. 2005 Jul 26;65(2):235-8 - PubMed
  145. Am J Respir Crit Care Med. 2001 Aug 15;164(4):669-71 - PubMed
  146. Br J Dermatol. 2010 Dec;163(6):1238-44 - PubMed
  147. Ren Fail. 2010;32(10):1233-6 - PubMed
  148. Cell Stem Cell. 2011 Nov 4;9(5):447-62 - PubMed
  149. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):E1070-9 - PubMed
  150. Dev Biol. 2006 Dec 15;300(2):656-69 - PubMed
  151. Development. 2003 Feb;130(3):483-94 - PubMed
  152. N Engl J Med. 2008 Jan 10;358(2):140-51 - PubMed

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