دورية أكاديمية
أعرض في EDS

Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in Human Huntington's Disease Neural Stem Cells.

التفاصيل البيبلوغرافية
العنوان: Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in Human Huntington's Disease Neural Stem Cells.
المؤلفون: Ring KL; Buck Institute for Research on Aging, Novato, CA 94945, USA., An MC; Buck Institute for Research on Aging, Novato, CA 94945, USA., Zhang N; Buck Institute for Research on Aging, Novato, CA 94945, USA., O'Brien RN; Buck Institute for Research on Aging, Novato, CA 94945, USA., Ramos EM; Departments of Neurology and Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA., Gao F; Departments of Neurology and Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA., Atwood R; Buck Institute for Research on Aging, Novato, CA 94945, USA., Bailus BJ; Buck Institute for Research on Aging, Novato, CA 94945, USA., Melov S; Buck Institute for Research on Aging, Novato, CA 94945, USA., Mooney SD; Buck Institute for Research on Aging, Novato, CA 94945, USA., Coppola G; Departments of Neurology and Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA., Ellerby LM; Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: lellerby@buckinstitute.org.
المصدر: Stem cell reports [Stem Cell Reports] 2015 Dec 08; Vol. 5 (6), pp. 1023-1038.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
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 Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2013-
مواضيع طبية MeSH: Transcriptome*, Huntington Disease/*pathology , Induced Pluripotent Stem Cells/*pathology , Neural Stem Cells/*pathology, Cell Line ; Gene Regulatory Networks ; Humans ; Huntingtin Protein ; Huntington Disease/genetics ; Huntington Disease/physiopathology ; Induced Pluripotent Stem Cells/metabolism ; Mutation ; Nerve Growth Factors/genetics ; Nerve Tissue Proteins/genetics ; Netrin-1 ; Neural Stem Cells/metabolism ; Neurogenesis ; Transforming Growth Factor beta/genetics ; Tumor Suppressor Proteins/genetics
مستخلص: We utilized induced pluripotent stem cells (iPSCs) derived from Huntington's disease (HD) patients as a human model of HD and determined that the disease phenotypes only manifest in the differentiated neural stem cell (NSC) stage, not in iPSCs. To understand the molecular basis for the CAG repeat expansion-dependent disease phenotypes in NSCs, we performed transcriptomic analysis of HD iPSCs and HD NSCs compared to isogenic controls. Differential gene expression and pathway analysis pointed to transforming growth factor β (TGF-β) and netrin-1 as the top dysregulated pathways. Using data-driven gene coexpression network analysis, we identified seven distinct coexpression modules and focused on two that were correlated with changes in gene expression due to the CAG expansion. Our HD NSC model revealed the dysregulation of genes involved in neuronal development and the formation of the dorsal striatum. The striatal and neuronal networks disrupted could be modulated to correct HD phenotypes and provide therapeutic targets.
(Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: F32 NS080551 United States NS NINDS NIH HHS; P30 NS062691 United States NS NINDS NIH HHS; R01 NS100529 United States NS NINDS NIH HHS; T32 AG000266 United States AG NIA NIH HHS
المشرفين على المادة: 0 (HTT protein, human)
0 (Huntingtin Protein)
0 (NTN1 protein, human)
0 (Nerve Growth Factors)
0 (Nerve Tissue Proteins)
0 (Transforming Growth Factor beta)
0 (Tumor Suppressor Proteins)
158651-98-0 (Netrin-1)
تواريخ الأحداث: Date Created: 20151215 Date Completed: 20161011 Latest Revision: 20181113
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4682390
DOI: 10.1016/j.stemcr.2015.11.005
PMID: 26651603
قاعدة البيانات: MEDLINE
الوصف
تدمد:2213-6711
DOI:10.1016/j.stemcr.2015.11.005