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

Research output: Contribution to journal › Journal article › Research › peer-review

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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, 2021, p. 2213-2227.

Research output: Contribution to journal › Journal article › Research › peer-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;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{d571e5001a6c4ff79b3708a415c03cef,
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 = "amyotrophic lateral sclerosis, FUS, HDAC6, microfluidic device, neurite outgrowth, neurite regrowth, neuromuscular junction, Tubastatin A",
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 = "Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
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 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

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 - amyotrophic lateral sclerosis

KW - FUS

KW - HDAC6

KW - microfluidic device

KW - neurite outgrowth

KW - neurite regrowth

KW - neuromuscular junction

KW - Tubastatin A

U2 - 10.1016/j.stemcr.2021.03.029

DO - 10.1016/j.stemcr.2021.03.029

M3 - Journal article

C2 - 33891869

AN - SCOPUS:85106626307

VL - 16

SP - 2213

EP - 2227

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 9

ER -

ID: 368622968