دورية أكاديمية
Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence.
العنوان: | Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence. |
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المؤلفون: | Ohashi M; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA., Korsakova E; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA., Allen D; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Lee P; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Fu K; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Vargas BS; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Cinkornpumin J; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Salas C; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Park JC; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Germanguz I; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Langerman J; Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA., Chronis C; Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA., Kuoy E; Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA., Tran S; Department of Integrative Biology and Physiology, UCLA, Los Angeles, CA 90095, USA., Xiao X; Department of Integrative Biology and Physiology, UCLA, Los Angeles, CA 90095, USA., Pellegrini M; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA., Plath K; Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA. Electronic address: kplath@mednet.ucla.edu., Lowry WE; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: blowry@mcdb.ucla.edu. |
المصدر: | Stem cell reports [Stem Cell Reports] 2018 May 08; Vol. 10 (5), pp. 1453-1463. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101611300 Publication Model: Print Cited Medium: Internet ISSN: 2213-6711 (Electronic) Linking ISSN: 22136711 NLM ISO Abbreviation: Stem Cell Reports |
أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2013- |
مواضيع طبية MeSH: | Cellular Senescence*, Methyl-CpG-Binding Protein 2/*deficiency , Neurons/*metabolism , Neurons/*pathology , Tumor Suppressor Protein p53/*metabolism, Brain/metabolism ; DNA Damage ; Dendrites/metabolism ; Gene Expression Regulation ; Humans ; Methyl-CpG-Binding Protein 2/metabolism ; Models, Biological ; Rett Syndrome/pathology ; Transcriptome/genetics |
مستخلص: | To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence. The induction of P53 appeared to affect dendritic branching in Rett neurons, as P53 inhibition restored dendritic complexity. The induction of P53 targets was also detectable in analyses of human Rett patient brain, suggesting that this disease-in-a-dish model can provide relevant insights into the human disorder. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.) |
References: | J Neurosci. 2009 Nov 18;29(46):14394-407. (PMID: 19923274) Cell. 1997 Feb 21;88(4):471-81. (PMID: 9038338) Cell Stem Cell. 2007 Jun 7;1(1):55-70. (PMID: 18371336) Cell Stem Cell. 2013 Oct 3;13(4):446-58. (PMID: 24094325) Cell. 2016 Oct 6;167(2):293-297. (PMID: 27716498) Nucleic Acids Res. 1992 Oct 11;20(19):5085-92. (PMID: 1408825) Cell Stem Cell. 2009 Feb 6;4(2):141-54. (PMID: 19200803) Neuron. 2015 Nov 18;88(4):651-8. (PMID: 26590342) Nat Methods. 2009 May;6(5):370-6. (PMID: 19404254) Hum Mol Genet. 2014 Dec 1;23(23):6366-74. (PMID: 25008110) Front Oncol. 2013 Feb 28;3:35. (PMID: 23450006) PLoS One. 2009 Dec 02;4(12):e8124. (PMID: 19956585) Cell. 2012 Dec 21;151(7):1417-30. (PMID: 23260135) J Pharmacol Exp Ther. 2018 May;365(2):291-300. (PMID: 29523700) Genes Dev. 2007 Dec 1;21(23):3110-22. (PMID: 18056424) Cell Stem Cell. 2016 Oct 6;19(4):476-490. (PMID: 27618217) Cell Rep. 2016 May 24;15(8):1809-21. (PMID: 27184841) Hum Mol Genet. 2011 Jun 1;20(11):2103-15. (PMID: 21372149) Cell Rep. 2016 Oct 18;17(4):1184-1192. (PMID: 27760320) PLoS One. 2011 Jan 27;6(1):e16478. (PMID: 21304588) Stem Cells. 2010 Apr;28(4):687-94. (PMID: 20166152) Cell Stem Cell. 2017 Jan 5;20(1):87-101. (PMID: 27989770) Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2883-8. (PMID: 18287077) Neuron. 2006 Oct 19;52(2):255-69. (PMID: 17046689) Methods Mol Biol. 2013;1048:135-44. (PMID: 23929103) Science. 2003 Oct 31;302(5646):885-9. (PMID: 14593183) Cell Rep. 2017 Jan 3;18(1):54-67. (PMID: 27989715) Cell Stem Cell. 2010 Sep 3;7(3):329-42. (PMID: 20727844) FASEB J. 2010 May;24(5):1593-603. (PMID: 20065105) Biochem Soc Trans. 2008 Aug;36(Pt 4):575-83. (PMID: 18631120) Nat Genet. 1997 Jul;16(3):256-9. (PMID: 9207790) Cell. 2006 Jan 13;124(1):207-19. (PMID: 16413492) Cell Res. 2012 Jan;22(1):178-93. (PMID: 21844894) Mutat Res. 2002 Feb 20;499(2):163-76. (PMID: 11827710) J Neurochem. 2014 Oct;131(1):115-27. (PMID: 24978323) Biogerontology. 2014 Dec;15(6):643-60. (PMID: 25305051) Cell. 2010 Nov 12;143(4):527-39. (PMID: 21074045) Nat Genet. 2001 Mar;27(3):327-31. (PMID: 11242118) Cell Stem Cell. 2013 May 2;12(5):559-72. (PMID: 23642365) Exp Gerontol. 1996 Jan-Apr;31(1-2):295-301. (PMID: 8706799) Cell Stem Cell. 2012 May 4;10(5):595-609. (PMID: 22560080) Stem Cell Reports. 2014 Nov 11;3(5):758-73. (PMID: 25316189) |
معلومات مُعتمدة: | P01 GM099134 United States GM NIGMS NIH HHS; P50 CA211015 United States CA NCI NIH HHS; T32 CA009056 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: MECP2; Rett syndrome; disease in a dish; senescence |
المشرفين على المادة: | 0 (Methyl-CpG-Binding Protein 2) 0 (Tumor Suppressor Protein p53) |
تواريخ الأحداث: | Date Created: 20180510 Date Completed: 20190806 Latest Revision: 20220408 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5995366 |
DOI: | 10.1016/j.stemcr.2018.04.001 |
PMID: | 29742391 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2213-6711 |
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DOI: | 10.1016/j.stemcr.2018.04.001 |