دورية أكاديمية
أعرض في EDS

Modeling and rescue of the vascular phenotype of Williams-Beuren syndrome in patient induced pluripotent stem cells.

التفاصيل البيبلوغرافية
العنوان: Modeling and rescue of the vascular phenotype of Williams-Beuren syndrome in patient induced pluripotent stem cells.
المؤلفون: Kinnear C; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada., Chang WY, Khattak S, Hinek A, Thompson T, de Carvalho Rodrigues D, Kennedy K, Mahmut N, Pasceri P, Stanford WL, Ellis J, Mital S
المصدر: Stem cells translational medicine [Stem Cells Transl Med] 2013 Jan; Vol. 2 (1), pp. 2-15. Date of Electronic Publication: 2012 Dec 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101578022 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2157-6564 (Print) Linking ISSN: 21576564 NLM ISO Abbreviation: Stem Cells Transl Med Subsets: MEDLINE
أسماء مطبوعة: Publication: 2022- : Oxford : Oxford University Press
Original Publication: Durham, NC : AlphaMed Press
مواضيع طبية MeSH: Induced Pluripotent Stem Cells/*physiology , Muscle, Smooth, Vascular/*pathology , Myocytes, Smooth Muscle/*metabolism , Williams Syndrome/*pathology, Antigens, Differentiation/genetics ; Antigens, Differentiation/metabolism ; Calcium Signaling ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Fibroblasts/metabolism ; Fibroblasts/physiology ; Hemizygote ; Human Umbilical Vein Endothelial Cells ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors/biosynthesis ; Male ; Muscle Contraction ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/physiology ; Octamer Transcription Factor-3/biosynthesis ; Peptide Fragments/pharmacology ; Phenotype ; Proto-Oncogene Proteins c-myc/biosynthesis ; Recombinant Proteins/biosynthesis ; SOXB1 Transcription Factors/biosynthesis ; Sequence Analysis, DNA ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; Transcriptome/drug effects ; Williams Syndrome/genetics
مستخلص: Elastin haploinsufficiency in Williams-Beuren syndrome (WBS) leads to increased vascular smooth muscle cell (SMC) proliferation and stenoses. Our objective was to generate a human induced pluripotent stem (hiPS) cell model for in vitro assessment of the WBS phenotype and to test the ability of candidate agents to rescue the phenotype. hiPS cells were reprogrammed from skin fibroblasts of a WBS patient with aortic and pulmonary stenosis and healthy control BJ fibroblasts using four-factor retrovirus reprogramming and were differentiated into SMCs. Differentiated SMCs were treated with synthetic elastin-binding protein ligand 2 (EBPL2) (20 μg/ml) or the antiproliferative drug rapamycin (100 nM) for 5 days. We generated four WBS induced pluripotent stem (iPS) cell lines that expressed pluripotency genes and differentiated into all three germ layers. Directed differentiation of BJ iPS cells yielded an 85%-92% pure SMC population that expressed differentiated SMC markers, were functionally contractile, and formed tube-like structures on three-dimensional gel assay. Unlike BJ iPS cells, WBS iPS cells generated immature SMCs that were highly proliferative, showed lower expression of differentiated SMC markers, reduced response to the vasoactive agonists, carbachol and endothelin-1, impaired vascular tube formation, and reduced calcium flux. EBPL2 partially rescued and rapamycin fully rescued the abnormal SMC phenotype by decreasing the smooth muscle proliferation rate and enhancing differentiation and tube formation. WBS iPS cell-derived SMCs demonstrate an immature proliferative phenotype with reduced functional and contractile properties, thereby recapitulating the human disease phenotype. The ability of rapamycin to rescue the phenotype provides an attractive therapeutic candidate for patients with WBS and vascular stenoses.
References: J Clin Invest. 1996 Nov 15;98(10):2277-83. (PMID: 8941644)
Nature. 2008 May 22;453(7194):524-8. (PMID: 18432194)
Am J Pathol. 2011 Sep;179(3):1560-72. (PMID: 21763677)
Hum Mol Genet. 2011 Jun 1;20(11):2103-15. (PMID: 21372149)
Nat Biotechnol. 2009 Nov;27(11):1033-7. (PMID: 19826408)
N Engl J Med. 2010 Dec 9;363(24):2310-9. (PMID: 21080780)
J Vasc Res. 1995 Mar-Apr;32(2):112-9. (PMID: 7734657)
Cell. 2010 Nov 12;143(4):527-39. (PMID: 21074045)
Nature. 2009 Jan 15;457(7227):277-80. (PMID: 19098894)
J Cell Biochem. 2011 Feb;112(2):723-33. (PMID: 21268094)
Circ Res. 2011 Feb 4;108(3):365-77. (PMID: 21293008)
Am J Med Genet C Semin Med Genet. 2010 May 15;154C(2):209-19. (PMID: 20425782)
J Struct Biol. 2001 Jan;133(1):43-54. (PMID: 11356063)
Pharmacol Ther. 2006 Sep;111(3):771-91. (PMID: 16488477)
N Engl J Med. 2007 Mar 8;356(10):1030-9. (PMID: 17296823)
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):33-8. (PMID: 18162540)
Circulation. 2009 Apr 21;119(15):2078-85. (PMID: 19349326)
Nature. 2010 Jun 10;465(7299):808-12. (PMID: 20535210)
Biochem Biophys Res Commun. 2011 Jul 8;410(3):531-6. (PMID: 21679692)
N Engl J Med. 2010 Jan 21;362(3):239-52. (PMID: 20089974)
Nat Biotechnol. 2012 Jan 15;30(2):165-73. (PMID: 22252507)
N Engl J Med. 2010 Oct 7;363(15):1397-409. (PMID: 20660394)
Cell Stem Cell. 2011 Jan 7;8(1):31-45. (PMID: 21185252)
Eur J Hum Genet. 2000 Dec;8(12):955-63. (PMID: 11175284)
Blood Press Monit. 2010 Oct;15(5):257-61. (PMID: 20729725)
Cell. 2009 May 15;137(4):647-58. (PMID: 19409607)
J Biol Chem. 2011 Dec 30;286(52):44926-36. (PMID: 22049077)
Wiley Interdiscip Rev Syst Biol Med. 2012 Jul-Aug;4(4):339-50. (PMID: 22492636)
Nature. 2011 Mar 10;471(7337):225-9. (PMID: 21240260)
Am J Med Genet A. 2004 Jun 15;127A(3):234-7. (PMID: 15150772)
J Biol Chem. 2002 Nov 22;277(47):44854-63. (PMID: 12244048)
J Biol Chem. 2010 Nov 26;285(48):37396-404. (PMID: 20847053)
Nature. 2009 Sep 17;461(7262):402-6. (PMID: 19693009)
J Biol Chem. 2007 Apr 27;282(17):12484-91. (PMID: 17327233)
J Clin Invest. 1998 Nov 15;102(10):1783-7. (PMID: 9819363)
Lab Invest. 2003 Dec;83(12):1811-20. (PMID: 14691299)
Lancet. 2002 Feb 16;359(9306):619-22. (PMID: 11867133)
J Soc Biol. 2001;195(2):157-64. (PMID: 11723828)
Eur Heart J. 1993 Nov;14(11):1458-64. (PMID: 8299625)
Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):e311-2. (PMID: 18029907)
EMBO Mol Med. 2009 Apr;1(1):50-65. (PMID: 20049703)
Nature. 2011 Mar 10;471(7337):230-4. (PMID: 21307850)
Circulation. 2001 Sep 4;104(10):1188-93. (PMID: 11535578)
Cell Adhes Commun. 1994 Jul;2(3):185-93. (PMID: 7827955)
J Biol Chem. 2011 Oct 21;286(42):36580-91. (PMID: 21880723)
Am J Hum Genet. 2002 Jul;71(1):30-44. (PMID: 12016585)
Nature. 2008 Apr 3;452(7187):548-52. (PMID: 18385728)
Circulation. 2012 Oct 2;126(14):1695-704. (PMID: 22914687)
Nature. 2009 Aug 6;460(7256):705-10. (PMID: 19578358)
Nat Protoc. 2009;4(12):1828-44. (PMID: 20010937)
Nat Biotechnol. 2012 Feb 08;30(2):152-4. (PMID: 22318032)
Eur J Hum Genet. 2011 Dec;19(12):1246-55. (PMID: 21750574)
Eur Heart J. 2006 Aug;27(15):1876-83. (PMID: 16731534)
Nature. 1998 May 21;393(6682):276-80. (PMID: 9607766)
Nature. 2011 Apr 14;472(7342):221-5. (PMID: 21346760)
Exp Hematol. 2010 Mar;38(3):246-257.e1. (PMID: 20067819)
Circ Res. 2007 Aug 31;101(5):523-31. (PMID: 17626896)
Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14169-74. (PMID: 21807996)
Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1248-58. (PMID: 17379839)
Nat Methods. 2009 May;6(5):370-6. (PMID: 19404254)
معلومات مُعتمدة: MOP-89910 Canada Canadian Institutes of Health Research
المشرفين على المادة: 0 (Antigens, Differentiation)
0 (Kruppel-Like Factor 4)
0 (Kruppel-Like Transcription Factors)
0 (MYC protein, human)
0 (Octamer Transcription Factor-3)
0 (POU5F1 protein, human)
0 (Peptide Fragments)
0 (Proto-Oncogene Proteins c-myc)
0 (Recombinant Proteins)
0 (SOX2 protein, human)
0 (SOXB1 Transcription Factors)
EC 2.7.1.1 (MTOR protein, human)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20130104 Date Completed: 20130208 Latest Revision: 20211203
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3659746
DOI: 10.5966/sctm.2012-0054
PMID: 23283491
قاعدة البيانات: MEDLINE
الوصف
تدمد:2157-6564
DOI:10.5966/sctm.2012-0054