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Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition. / Stoklund Dittlau, Katarina; Krasnow, Emily N.; Fumagalli, Laura; Vandoorne, Tijs; Baatsen, Pieter; Kerstens, Axelle; Giacomazzi, Giorgia; Pavie, Benjamin; Rossaert, Elisabeth; Beckers, Jimmy; Sampaolesi, Maurilio; van Damme, Philip; van den Bosch, Ludo.

In: Stem cell reports, Vol. 16, No. 9, 14.09.2021, p. 2213-2227.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Stoklund Dittlau, K, Krasnow, EN, Fumagalli, L, Vandoorne, T, Baatsen, P, Kerstens, A, Giacomazzi, G, Pavie, B, Rossaert, E, Beckers, J, Sampaolesi, M, van Damme, P & van den Bosch, L 2021, 'Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition', Stem cell reports, vol. 16, no. 9, pp. 2213-2227. https://doi.org/10.1016/j.stemcr.2021.03.029

APA

Stoklund Dittlau, K., Krasnow, E. N., Fumagalli, L., Vandoorne, T., Baatsen, P., Kerstens, A., Giacomazzi, G., Pavie, B., Rossaert, E., Beckers, J., Sampaolesi, M., van Damme, P., & van den Bosch, L. (2021). Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition. Stem cell reports, 16(9), 2213-2227. https://doi.org/10.1016/j.stemcr.2021.03.029

Vancouver

Stoklund Dittlau K, Krasnow EN, Fumagalli L, Vandoorne T, Baatsen P, Kerstens A et al. Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition. Stem cell reports. 2021 Sep 14;16(9):2213-2227. https://doi.org/10.1016/j.stemcr.2021.03.029

Author

Stoklund Dittlau, Katarina ; Krasnow, Emily N. ; Fumagalli, Laura ; Vandoorne, Tijs ; Baatsen, Pieter ; Kerstens, Axelle ; Giacomazzi, Giorgia ; Pavie, Benjamin ; Rossaert, Elisabeth ; Beckers, Jimmy ; Sampaolesi, Maurilio ; van Damme, Philip ; van den Bosch, Ludo. / Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition. In: Stem cell reports. 2021 ; Vol. 16, No. 9. pp. 2213-2227.

BibTeX

@article{7c15c290a4584de18ffb8c826bbcfaff,
title = "Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition",
abstract = "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.",
keywords = "FUS, HDAC6, Tubastatin A, amyotrophic lateral sclerosis, microfluidic device, neurite outgrowth, neurite regrowth, neuromuscular junction",
author = "{Stoklund Dittlau}, Katarina and Krasnow, {Emily N.} and Laura Fumagalli and Tijs Vandoorne and Pieter Baatsen and Axelle Kerstens and Giorgia Giacomazzi and Benjamin Pavie and Elisabeth Rossaert and Jimmy Beckers and Maurilio Sampaolesi and {van Damme}, Philip and {van den Bosch}, Ludo",
note = "Funding Information: The authors thank Sebastian Munck and Nikky Corthout from LiMoNe, Research Group Molecular Neurobiology (VIB-KU Leuven) for discussions concerning Ca 2+ live-cell imaging. This research was supported by the Fulbright Commission to Belgium and Luxembourg, the VIB, the KU Leuven (C1 and “Opening the Future” Fund), the “Fund for Scientific Research Flanders” (FWO-Vlaanderen), the Agency for Innovation by Science and Technology (IWT; SBO-iPSCAF), the Belgian Government (Interuniversity Attraction Poles Program P7/16 initiated by the Belgian Federal Science Policy Office ), the Thierry Latran Foundation , the “Association Belge contre les Maladies neuro-Musculaires” (ABMM), Target ALS, and the ALS Liga Belgi{\"e} (A Cure for ALS). T.V., E.R., and J.B. are supported by strategic basic research PhD fellowships awarded by FWO-Vlaanderen. Publisher Copyright: {\textcopyright} 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = sep,
day = "14",
doi = "10.1016/j.stemcr.2021.03.029",
language = "English",
volume = "16",
pages = "2213--2227",
journal = "Stem cell reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

T1 - Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition

AU - Stoklund Dittlau, Katarina

AU - Krasnow, Emily N.

AU - Fumagalli, Laura

AU - Vandoorne, Tijs

AU - Baatsen, Pieter

AU - Kerstens, Axelle

AU - Giacomazzi, Giorgia

AU - Pavie, Benjamin

AU - Rossaert, Elisabeth

AU - Beckers, Jimmy

AU - Sampaolesi, Maurilio

AU - van Damme, Philip

AU - van den Bosch, Ludo

N1 - Funding Information: The authors thank Sebastian Munck and Nikky Corthout from LiMoNe, Research Group Molecular Neurobiology (VIB-KU Leuven) for discussions concerning Ca 2+ live-cell imaging. This research was supported by the Fulbright Commission to Belgium and Luxembourg, the VIB, the KU Leuven (C1 and “Opening the Future” Fund), the “Fund for Scientific Research Flanders” (FWO-Vlaanderen), the Agency for Innovation by Science and Technology (IWT; SBO-iPSCAF), the Belgian Government (Interuniversity Attraction Poles Program P7/16 initiated by the Belgian Federal Science Policy Office ), the Thierry Latran Foundation , the “Association Belge contre les Maladies neuro-Musculaires” (ABMM), Target ALS, and the ALS Liga België (A Cure for ALS). T.V., E.R., and J.B. are supported by strategic basic research PhD fellowships awarded by FWO-Vlaanderen. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9/14

Y1 - 2021/9/14

N2 - 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.

AB - 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.

KW - FUS

KW - HDAC6

KW - Tubastatin A

KW - amyotrophic lateral sclerosis

KW - microfluidic device

KW - neurite outgrowth

KW - neurite regrowth

KW - neuromuscular junction

UR - http://www.scopus.com/inward/record.url?scp=85106626307&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2021.03.029

DO - 10.1016/j.stemcr.2021.03.029

M3 - Article

C2 - 33891869

VL - 16

SP - 2213

EP - 2227

JO - Stem cell reports

JF - Stem cell reports

SN - 2213-6711

IS - 9

ER -

ID: 18487390