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

Posted on: 12th March 2018

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published.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

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

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

    Register here

    Also in the cell biology category:

    Microtubules Gate Tau Condensation to Spatially Regulate Microtubule Functions

    Ruensern Tan, Aileen J. Lam, Tracy Tan, et al.

    AND

    Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes

    Valerie Siahaan, Jochen Krattenmacher, Amayra Hernandez-Vega, et al.



    Selected by Satish Bodakuntla

    The modular mechanism of chromocenter formation in Drosophila

    Madhav Jagannathan, Ryan Cummings, Yukiko M Yamashita



    Selected by Maiko Kitaoka

    1

    The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis.

    Joseph Franics McKenna, Daniel Rolfe, Stephen E D Webb, et al.



    Selected by Marc Somssich

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    Old fibroblasts secrete inflammatory cytokines that drive variability in reprogramming efficiency and may affect wound healing between old individuals

    Salah Mahmoudi, Elena Mancini, Alessandra Moore, et al.



    Selected by Shikha Nayar

    DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction

    Joshua A. Weinstein, Aviv Regev, Feng Zhang



    Selected by Theo Sanderson

    2

    The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner

    Federico Germani, Daniel Hain, Denise Sternlicht, et al.



    Selected by Rohan Khadilkar

    Drosophila kinesin-8 stabilises kinetochore-microtubule interaction

    Tomoya Edzuka, Gohta Goshima



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    1

    Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma.

    Andrea Palamidessi, Chiara Malinverno, Emanuela FRITTOLI, et al.



    Selected by Tim Fessenden

    1

    Tension on kinetochore substrates is insufficient to prevent Aurora-triggered detachment

    Anna K de Regt, Charles L Asbury, Sue Biggins



    Selected by Angika Basant

    1

    Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

    Sandra Ruiz Garcia, Marie Deprez, Kevin Lebrigand, et al.



    Selected by Rob Hynds

    1

    Actomyosin-driven tension at compartmental boundaries orients cell division independently of cell geometry in vivo

    Elena Scarpa, Cedric Finet, Guy Blanchard, et al.



    Selected by Ivana Viktorinová

    Molecular organization of integrin-based adhesion complexes in mouse Embryonic Stem Cells

    Shumin Xia, Evelyn K.F. Yim, Pakorn Kanchanawong

    AND

    Superresolution architecture of pluripotency guarding adhesions

    Aki Stubb, Camilo Guzmán, Elisa Närvä, et al.



    Selected by Nicola Stevenson, Amanda Haage

    Transcriptional initiation and mechanically driven self-propagation of a tissue contractile wave during axis elongation

    Anais Bailles, Claudio Collinet, Jean-Marc Philippe, et al.



    Selected by Sundar Naganathan

    1

    Bridging the divide: bacteria synthesizing archaeal membrane lipids

    Laura Villanueva, F. A. Bastiaan von Meijenfeldt, Alexander B. Westbye, et al.

    AND

    Extensive transfer of membrane lipid biosynthetic genes between Archaea and Bacteria

    Gareth A. Coleman, Richard D. Pancost, Tom A. Williams



    Selected by Gautam Dey

    1

    Revealing the nanoscale morphology of the primary cilium using super-resolution fluorescence microscopy

    Joshua Yoon, Colin J. Comerci, Lucien E. Weiss, et al.



    Selected by Gautam Dey

    Also in the developmental biology category:

    The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis.

    Joseph Franics McKenna, Daniel Rolfe, Stephen E D Webb, et al.



    Selected by Marc Somssich

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    A Scube2-Shh feedback loop links morphogen release to morphogen signaling to enable scale invariant patterning of the ventral neural tube

    Zach Collins, Kana Ishimatsu, Tony Tsai, et al.



    Selected by Teresa Rayon

    1

    Epiblast formation by Tead-Yap-dependent expression of pluripotency factors and competitive elimination of unspecified cells

    Masakazu Hashimoto, Hiroshi Sasaki



    Selected by Sarah Bowling, Teresa Rayon

    Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

    Julien Delile, Teresa Rayon, Manuela Melchionda, et al.



    Selected by Reena Lasrado

    1

    The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner

    Federico Germani, Daniel Hain, Denise Sternlicht, et al.



    Selected by Rohan Khadilkar

    Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila

    Charles A Seller, Chun-Yi Cho, Patrick H O'Farrell



    Selected by Gabriel Aughey

    A histidine kinase gene is required for large radius root tip circumnutation and surface exploration in rice

    Kevin R Lehner, Isaiah Taylor, Erin N McCaskey, et al.



    Selected by Martin Balcerowicz

    Actomyosin-driven tension at compartmental boundaries orients cell division independently of cell geometry in vivo

    Elena Scarpa, Cedric Finet, Guy Blanchard, et al.



    Selected by Ivana Viktorinová

    Molecular organization of integrin-based adhesion complexes in mouse Embryonic Stem Cells

    Shumin Xia, Evelyn K.F. Yim, Pakorn Kanchanawong

    AND

    Superresolution architecture of pluripotency guarding adhesions

    Aki Stubb, Camilo Guzmán, Elisa Närvä, et al.



    Selected by Nicola Stevenson, Amanda Haage

    Transcriptional initiation and mechanically driven self-propagation of a tissue contractile wave during axis elongation

    Anais Bailles, Claudio Collinet, Jean-Marc Philippe, et al.



    Selected by Sundar Naganathan

    1

    Signaling dynamics control cell fate in the early Drosophila embryo

    Heath E Johnson, Stanislav Y Shvartsman, Jared E Toettcher



    Selected by Yara E. Sánchez Corrales

    1

    Three-dimensional tissue stiffness mapping in the mouse embryo supports durotaxis during early limb bud morphogenesis

    Min Zhu, Hirotaka Tao, Mohammad Samani, et al.



    Selected by Natalie Dye

    PUMILIO hyperactivity drives premature aging of Norad-deficient mice

    Florian Kopp, Mehmet Yalvac, Beibei Chen, et al.



    Selected by Carmen Adriaens

    Synergy with TGFβ ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation

    Joseph Massey, Yida Liu, Omar Alvarenga, et al.



    Selected by Pierre Osteil

    1

    3D Tissue elongation via ECM stiffness-cued junctional remodeling

    Dong-Yuan Chen, Justin Crest, Sebastian J Streichan, et al.



    Selected by Sundar Naganathan
    Close