Menu

Close

A 3D model of human skeletal muscle innervated with stem cell-derived motor neurons enables epsilon-subunit targeted myasthenic syndrome studies

Mohsen Afshar Bakooshli, Ethan S Lippmann, Ben Mulcahy, Kayee Tung, Elena Pegoraro, Henry Ahn, Howard Ginsberg, Mei Zhen, Randolph S Ashton, Penney M Gilbert

Preprint posted on March 03, 2018 https://www.biorxiv.org/content/early/2018/03/03/275545

A novel 3D co-culture system has been developed that can recapitulate human adult neuromuscular junctions in vitro

Selected by Chris Demers

Background: Neuromuscular diseases are complex and devastating diseases, which in many cases only become symptomatic later in adult lives. Scientists have thus far failed to develop a biologically relevant model of adult human neuromuscular junctions, a critical site of disease pathogenesis. Such a platform would enable the study of not only the fundamental biology underpinning these diseases, but also provide a platform to test potential therapies.

Key Findings: This preprint represents the first example of an in vitro culture system that can be used to study adult human neuromuscular junctions. Critically, the authors found that the system only worked when cells were grown in 3D culture, as their 2D counterparts failed to undergo the critical developmental switch in acetylcholine receptors that is a hallmark of mature adult motor neurons.

Fig 1. Microdevice Overview

Skeletal muscle precursors and stem cell derived motor neuron precursors were mixed in a fibrin/Geltrex™ hydrogel and placed in a PDMS microchannel with Velcro™ anchors for support. Over the course of just two-weeks the two populations self-organized and formed functional neuromuscular junctions. These junctions demonstrated many of the hallmarks of motor neuron innervated muscles, including localised calcium transients upon stimulation with glutamate.

Why I Chose This: I find it remarkable that stem cells have an inherent ability to self-organize into physiologically relevant structures. In most cases all that is required are the appropriate boundary conditions, be it soluble (i.e. addition of morphogens) or physical. In this preprint, by constraining cells to a three-dimensional microenvironment the authors were able to guide cells into forming functional, innervated muscles.

 

Open Questions:

  • What are the unique aspects of the 3D culture conditions that lead to the maturation of the motor neurons?
  • Is cell density a critical parameter to obtain reproducible results?
  • Can the system be used with other motor neuron subtypes (i.e. MMC vs. LMC) and/or other muscle subtypes?

Tags: nmj, stem cell

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the cell biology category:

    Spatiotemporally controlled Myosin relocalization and internal pressure cause biased cortical extension to generate sibling cell size asymmetry

    Tri Thanh Pham, Arnaud Monnard, Jonne Helenius, et al.



    Selected by Giuliana Clemente

    Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading

    Hamish T J Gilbert, Venkatesh Mallikarjun, Oana Dobre, et al.



    Selected by Rebecca Quelch

    1

    A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins

    David Booth, Heather Middleton, Nicole King



    Selected by Maya Emmons-Bell

    SWI/SNF remains localized to chromatin in the presence of SCHLAP1

    Jesse R Raab, Keriayn N Smith, Camarie C Spear, et al.



    Selected by Carmen Adriaens

    1

    Clathrin plaques form mechanotransducing platforms

    Agathe Franck, Jeanne Laine, Gilles Moulay, et al.



    Selected by Amanda Haage

    Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

    Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, et al.



    Selected by Helen Weavers

    A non-cell autonomous actin redistribution enables isotropic retinal growth

    Marija Matejcic, Guillaume Salbreux, Caren Norden



    Selected by Yara E. Sánchez Corrales

    1

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Arnaud Monnard

    1

    Optogenetic reconstitution reveals that Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura, Toyoaki Natsume, Masato T Kanemaki, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes

    Pierre ROME, Hiroyuki OHKURA



    Selected by Binyam Mogessie

    ERM proteins: The missing actin linkers in clathrin-mediated endocytosis

    Audun Sverre Kvalvaag, Kay Oliver Schink, Andreas Brech, et al.



    Selected by Nicola Stevenson

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    A non-canonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

    Saipraveen Srinivasan, Christoph J. Burckhardt, Madhura Bhave, et al.



    Selected by Penelope La-Borde

    Atomic model of microtubule-bound tau

    Elizabeth H Kellogg, Nisreen M.A. Hejab, Simon Poepsel, et al.



    Selected by Satish Bodakuntla

    1

    Also in the developmental biology category:

    Human macrophages survive and adopt activated genotypes in living zebrafish

    Colin D. Paul, Alexus Devine, Kevin Bishop, et al.



    Selected by Giuliana Clemente

    Altering the temporal regulation of one transcription factor drives sensory trade-offs

    Ariane Ramaekers, Simon Weinberger, Annelies Claeys, et al.



    Selected by Mariana R.P. Alves

    Presence of midline cilia supersedes the expression of Lefty1 in forming the midline barrier during the establishment of left-right asymmetry

    Natalia A Shylo, Dylan A Ramrattan, Scott D Weatherbee



    Selected by Hannah Brunsdon

    Genetic compensation is triggered by mutant mRNA degradation

    Mohamed El-Brolosy, Andrea Rossi, Zacharias Kontarakis, et al.



    Selected by Andreas van Impel

    1

    Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

    Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, et al.



    Selected by Helen Weavers

    Photoperiod sensing of the circadian clock is controlled by ELF3 and GI

    Usman Anwer, Amanda Davis, Seth Jon Davis, et al.



    Selected by Annika Weimer

    Limb- and tendon-specific Adamtsl2 deletion identifies a soft tissue mechanism modulating bone length

    Dirk Hubmacher, Stetson Thacker, Sheila M Adams, et al.



    Selected by Alberto Rosello-Diez

    A non-cell autonomous actin redistribution enables isotropic retinal growth

    Marija Matejcic, Guillaume Salbreux, Caren Norden



    Selected by Yara E. Sánchez Corrales

    1

    Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance in Daphnia

    Dominik Martin-Creuzburg, Bret L. Coggins, Dieter Ebert, et al.



    Selected by Alexander Little

    A SoxB gene acts as an anterior gap gene and regulates posterior segment addition in the spider Parasteatoda tepidariorum

    Christian L. B. Paese, Anna Schoenauer, Daniel J. Leite, et al.



    Selected by Erik Clark

    1

    Cell type-specific interchromosomal interactions as a mechanism for transcriptional diversity

    Adan Horta, Kevin Monahan, Lisa Bashkirova, et al.



    Selected by Boyan Bonev

    Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm.

    Miguel Salinas-Saavedra, Amber Q. Rock, Mark Q. Martindale



    Selected by ClaireS & SophieM

    1

    Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development

    Andrew J Aman, Alexis N Fulbright, David M Parichy



    Selected by Andreas van Impel

    Tissue flow induces cell shape changes during organogenesis

    Gonca Erdemci-Tandogan, Madeline J.Clark, Jeffrey D. Amack, et al.



    Selected by Jacky G. Goetz

    Temporal Control of Transcription by Zelda in living Drosophila embryos

    Jeremy Dufourt, Antonio Trullo, Jennifer Hunter, et al.



    Selected by Teresa Rayon

    1

    An atlas of silencer elements for the human and mouse genomes

    Naresh Doni Jayavelu, Ajay Jajodia, Arpit Mishra, et al.



    Selected by Rafael Galupa

    1

    Close

    We want to make our website, and the services we provide, useful and reliable. This sometimes involves placing small amounts of information called cookies on the device you used to access the internet. If you continue to use this website we will assume you are happy to accept our cookies.

    Accept