دورية أكاديمية
Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.
العنوان: | Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment. |
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المؤلفون: | Adams JW; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA; Center for Academic Research and Training in Anthropogeny, University of California, San Diego, La Jolla, CA 92093, USA., Vinokur A; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA., de Souza JS; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA., Austria C; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA., Guerra BS; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Experimental Multiuser Laboratory, Pontifícia Universidade Católica do Paraná, Curitiba, PR 80215-901, Brazil., Herai RH; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Experimental Multiuser Laboratory, Pontifícia Universidade Católica do Paraná, Curitiba, PR 80215-901, Brazil., Wahlin KJ; Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA., Muotri AR; Department of Pediatrics/Rady Children's Hospital, Department of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA; Center for Academic Research and Training in Anthropogeny, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: muotri@ucsd.edu. |
المصدر: | Cell reports [Cell Rep] 2024 Mar 26; Vol. 43 (3), pp. 113867. Date of Electronic Publication: 2024 Feb 27. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
مواضيع طبية MeSH: | Williams Syndrome*/genetics , Williams Syndrome*/metabolism , Transcription Factors, TFIII*/metabolism , Transcription Factors, TFII*/genetics , Transcription Factors, TFII*/metabolism, Humans ; Neurons/metabolism ; Social Behavior ; Phenotype |
مستخلص: | Individuals with Williams syndrome (WS), a neurodevelopmental disorder caused by hemizygous loss of 26-28 genes at 7q11.23, characteristically portray a hypersocial phenotype. Copy-number variations and mutations in one of these genes, GTF2I, are associated with altered sociality and are proposed to underlie hypersociality in WS. However, the contribution of GTF2I to human neurodevelopment remains poorly understood. Here, human cellular models of neurodevelopment, including neural progenitors, neurons, and three-dimensional cortical organoids, are differentiated from CRISPR-Cas9-edited GTF2I-knockout (GTF2I-KO) pluripotent stem cells to investigate the role of GTF2I in human neurodevelopment. GTF2I-KO progenitors exhibit increased proliferation and cell-cycle alterations. Cortical organoids and neurons demonstrate increased cell death and synaptic dysregulation, including synaptic structural dysfunction and decreased electrophysiological activity on a multielectrode array. Our findings suggest that changes in synaptic circuit integrity may be a prominent mediator of the link between alterations in GTF2I and variation in the phenotypic expression of human sociality. Competing Interests: Declaration of interests A.R.M. is a cofounder and has equity interest in TISMOO, a company dedicated to genetic analysis and brain organoid modeling focusing on therapeutic applications customized for ASD and other neurological disorders with genetic origins. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
References: | Bioinformatics. 2012 Aug 15;28(16):2184-5. (PMID: 22743226) Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2725-34. (PMID: 25870293) Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W741-8. (PMID: 15980575) J Autism Dev Disord. 2012 Jul;42(7):1459-69. (PMID: 22048961) Am J Med Genet A. 2004 Jan 30;124A(3):263-73. (PMID: 14708099) Mol Psychiatry. 2015 Nov;20(11):1350-65. (PMID: 25385366) Autism Res. 2011 Feb;4(1):28-39. (PMID: 21328569) Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700) Cell Stem Cell. 2019 Oct 3;25(4):558-569.e7. (PMID: 31474560) Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13030-5. (PMID: 14557539) Toxicol Sci. 2019 Jan 1;167(1):58-76. (PMID: 30169818) Front Psychol. 2012 May 30;3:168. (PMID: 22661963) Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15672-7. (PMID: 26644564) Nature. 2019 Sep;573(7772):61-68. (PMID: 31435019) J Neurosci. 2021 Dec 8;41(49):10034-10053. (PMID: 34663629) Nature. 2011 Oct 26;478(7370):483-9. (PMID: 22031440) BMC Neurosci. 2014 Nov 28;15:127. (PMID: 25429715) Nat Neurosci. 2016 Apr 26;19(6):647-655. (PMID: 29323671) Nature. 2016 Aug 18;536(7616):338-43. (PMID: 27509850) BMC Med Genet. 2010 Apr 19;11:61. (PMID: 20403157) Neuroscience. 2004;123(4):931-8. (PMID: 14751286) Physiology (Bethesda). 2019 Sep 1;34(5):365-375. (PMID: 31389776) N Engl J Med. 2010 Jan 21;362(3):239-52. (PMID: 20089974) Nucleic Acids Res. 2019 Jul 2;47(W1):W199-W205. (PMID: 31114916) Genome Biol. 2014;15(12):550. (PMID: 25516281) Mol Neurobiol. 2019 May;56(5):3313-3325. (PMID: 30120731) Mol Cell Biol. 2001 May;21(9):3220-33. (PMID: 11287625) J Mol Evol. 2013 Feb;76(1-2):28-47. (PMID: 23229069) Science. 2021 Feb 12;371(6530):. (PMID: 33574182) J Cogn Neurosci. 2000;12 Suppl 1:7-29. (PMID: 10953231) Gene. 2001 Aug 22;274(1-2):1-13. (PMID: 11674993) Biochim Biophys Acta. 2007 Nov-Dec;1769(11-12):613-21. (PMID: 17976384) N Engl J Med. 2005 Oct 20;353(16):1694-701. (PMID: 16236740) Mol Psychiatry. 2021 Nov;26(11):7047-7068. (PMID: 33888873) Cell Rep. 2016 Dec 20;17(12):3369-3384. (PMID: 28009303) Clin Genet. 1984 May;25(5):422-8. (PMID: 6723102) Trends Mol Med. 2017 Jun;23(6):501-511. (PMID: 28461154) Nat Genet. 2015 Feb;47(2):132-41. (PMID: 25501393) Cell. 2018 Nov 1;175(4):1088-1104.e23. (PMID: 30318146) Mol Cell Biol. 2005 Dec;25(24):10940-52. (PMID: 16314517) Genome Res. 2005 Sep;15(9):1179-88. (PMID: 16140988) Front Psychol. 2019 Mar 18;10:521. (PMID: 30936846) Nat Rev Dis Primers. 2021 Jun 17;7(1):42. (PMID: 34140529) Cell Stem Cell. 2020 Feb 6;26(2):221-233.e6. (PMID: 32004479) Brain. 2022 Jun 30;145(6):1962-1977. (PMID: 34957478) Science. 2003 May 2;300(5620):767-72. (PMID: 12690205) Mol Psychiatry. 2021 Dec;26(12):7560-7580. (PMID: 34433918) Nat Neurosci. 2019 May;22(5):700-708. (PMID: 31011227) Mol Cell Probes. 2018 Aug;40:45-51. (PMID: 29305905) Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886) Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):181-6. (PMID: 19109438) Mol Psychiatry. 2016 Feb;21(2):178-88. (PMID: 26347316) Front Cell Dev Biol. 2021 Nov 16;9:764725. (PMID: 34869356) J Med Genet. 2007 Jul;44(7):452-8. (PMID: 17400790) Am J Med Genet A. 2015 Dec;167A(12):2916-35. (PMID: 26333794) Cell Cycle. 2006 Feb;5(4):356-9. (PMID: 16479156) Am J Med Genet A. 2009 Mar;149A(3):302-14. (PMID: 19205026) EMBO Mol Med. 2021 Jan 11;13(1):e12523. (PMID: 33501759) Mol Neurobiol. 2020 Feb;57(2):765-777. (PMID: 31471877) Nat Genet. 2001 Nov;29(3):321-5. (PMID: 11685205) Nature. 2004 Nov 18;432(7015):298-306. (PMID: 15549091) J Cell Biochem. 2018 Jan;119(1):712-722. (PMID: 28657656) Mol Biol Evol. 2021 Oct 27;38(11):4748-4764. (PMID: 34132815) Nature. 2011 Mar 3;471(7336):63-7. (PMID: 21368825) |
معلومات مُعتمدة: | R01 MH127077 United States MH NIMH NIH HHS; DP2 OD006495 United States OD NIH HHS; R01 DA056908 United States DA NIDA NIH HHS; R01 MH123828 United States MH NIMH NIH HHS; S10 OD026929 United States OD NIH HHS; R01 ES033636 United States ES NIEHS NIH HHS; R56 MH109587 United States MH NIMH NIH HHS; U19 MH107367 United States MH NIMH NIH HHS; R21 MH128827 United States MH NIMH NIH HHS; T32 GM007198 United States GM NIGMS NIH HHS; R01 NS105969 United States NS NINDS NIH HHS; R01 HD107788 United States HD NICHD NIH HHS; R01 MH100175 United States MH NIMH NIH HHS; R01 HG012351 United States HG NHGRI NIH HHS; R01 NS123642 United States NS NINDS NIH HHS; R01 EY031318 United States EY NEI NIH HHS; R01 AG078959 United States AG NIA NIH HHS; R21 HD109616 United States HD NICHD NIH HHS |
فهرسة مساهمة: | Keywords: CP: Developmental biology; CP: Neuroscience; GTF2I; Williams syndrome; brain organoid; cortical organoid; neurodevelopment; stem cells |
المشرفين على المادة: | 0 (Transcription Factors, TFIII) 0 (GTF2I protein, human) 0 (Transcription Factors, TFII) |
تواريخ الأحداث: | Date Created: 20240228 Date Completed: 20240401 Latest Revision: 20240617 |
رمز التحديث: | 20240617 |
مُعرف محوري في PubMed: | PMC11002531 |
DOI: | 10.1016/j.celrep.2024.113867 |
PMID: | 38416640 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2211-1247 |
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DOI: | 10.1016/j.celrep.2024.113867 |