دورية أكاديمية
أعرض في EDS

Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition.

التفاصيل البيبلوغرافية
العنوان: Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition.
المؤلفون: Stoklund Dittlau K; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium., Krasnow EN; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium., Fumagalli L; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium., Vandoorne T; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium., Baatsen P; VIB, Center for Brain & Disease Research, Research Group Molecular Neurobiology, Leuven, Belgium; KU Leuven - University of Leuven, VIB Bio Imaging Core, Leuven, Belgium., Kerstens A; VIB, Center for Brain & Disease Research, Research Group Molecular Neurobiology, Leuven, Belgium; KU Leuven - University of Leuven, VIB Bio Imaging Core, Leuven, Belgium., Giacomazzi G; KU Leuven - University of Leuven, Department of Development and Regeneration, Stem Cell and Developmental Biology, Leuven, Belgium., Pavie B; VIB, Center for Brain & Disease Research, Research Group Molecular Neurobiology, Leuven, Belgium; KU Leuven - University of Leuven, VIB Bio Imaging Core, Leuven, Belgium., Rossaert E; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium., Beckers J; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium., Sampaolesi M; KU Leuven - University of Leuven, Department of Development and Regeneration, Stem Cell and Developmental Biology, Leuven, Belgium., Van Damme P; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium; University Hospitals Leuven, Department of Neurology, Leuven, Belgium., Van Den Bosch L; KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium. Electronic address: ludo.vandenbosch@kuleuven.be.
المصدر: Stem cell reports [Stem Cell Reports] 2021 Sep 14; Vol. 16 (9), pp. 2213-2227. Date of Electronic Publication: 2021 Apr 22.
نوع المنشور: Journal Article; 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-Electronic 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: Lab-On-A-Chip Devices* , Mutation*, Histone Deacetylase 6/*antagonists & inhibitors , Histone Deacetylase Inhibitors/*pharmacology , Neuromuscular Junction/*genetics , Neuromuscular Junction/*physiopathology , RNA-Binding Protein FUS/*genetics, Agrin/metabolism ; Amyotrophic Lateral Sclerosis/etiology ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Biomarkers ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Coculture Techniques ; Fluorescent Antibody Technique ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Laminin/metabolism ; Microfluidic Analytical Techniques ; Motor Neurons/cytology ; Motor Neurons/drug effects ; Motor Neurons/metabolism ; Muscle Fibers, Skeletal/cytology ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Neuromuscular Junction/drug effects ; Neuronal Outgrowth/drug effects
مستخلص: Neuromuscular junctions (NMJs) ensure communication between motor neurons (MNs) and muscle; however, in MN disorders, such as amyotrophic lateral sclerosis (ALS), NMJs degenerate resulting in muscle atrophy. The aim of this study was to establish a versatile and reproducible in vitro model of a human motor unit to investigate the effects of ALS-causing mutations. Therefore, we generated a co-culture of human induced pluripotent stem cell (iPSC)-derived MNs and human primary mesoangioblast-derived myotubes in microfluidic devices. A chemotactic and volumetric gradient facilitated the growth of MN neurites through microgrooves resulting in the interaction with myotubes and the formation of NMJs. We observed that ALS-causing FUS mutations resulted in reduced neurite outgrowth as well as an impaired neurite regrowth upon axotomy. NMJ numbers were likewise reduced in the FUS-ALS model. Interestingly, the selective HDAC6 inhibitor, Tubastatin A, improved the neurite outgrowth, regrowth, and NMJ morphology, prompting HDAC6 inhibition as a potential therapeutic strategy for ALS.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: FUS; HDAC6; Tubastatin A; amyotrophic lateral sclerosis; microfluidic device; neurite outgrowth; neurite regrowth; neuromuscular junction
المشرفين على المادة: 0 (Agrin)
0 (Biomarkers)
0 (FUS protein, human)
0 (Histone Deacetylase Inhibitors)
0 (Laminin)
0 (RNA-Binding Protein FUS)
EC 3.5.1.98 (HDAC6 protein, human)
EC 3.5.1.98 (Histone Deacetylase 6)
تواريخ الأحداث: Date Created: 20210423 Date Completed: 20220309 Latest Revision: 20220309
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8452598
DOI: 10.1016/j.stemcr.2021.03.029
PMID: 33891869
قاعدة البيانات: MEDLINE
الوصف
تدمد:2213-6711
DOI:10.1016/j.stemcr.2021.03.029