Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

  1. Alwyn Dady  Is a corresponding author
  2. Lindsay Davidson
  3. Pamela A Halley
  4. Kate G Storey  Is a corresponding author
  1. University of Dundee, United Kingdom

Abstract

Species-specific differentiation pace in-vitro indicates that some aspects of neural differentiation are governed by cell intrinsic properties. Here we describe a novel in-vitro human neural-rosette assay that recapitulates dorsal spinal cord differentiation but proceeds more rapidly than in the human embryo, suggesting that it lacks endogenous signalling dynamics. To test whether in-vitro conditions represent an intrinsic differentiation pace, human iPSC-derived neural rosettes were challenged by grafting into the faster differentiating chicken embryonic neural tube iso-chronically, or hetero-chronically into older embryos. In both contexts in-vitro differentiation pace was initially unchanged, while long-term analysis revealed iso-chronic slowed and hetero-chronic conditions promoted human neural differentiation. Moreover hetero-chronic conditions did not alter the human neural differentiation programme, which progressed to neurogenesis, while the host embryo advanced into gliogenesis. This study demonstrates that intrinsic properties limit human differentiation pace, and that timely extrinsic signals are required for progression through an intrinsic human neural differentiation programme.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data (all numerical meta data) are provided as excel tables aligned to the relevant figure.

Article and author information

Author details

  1. Alwyn Dady

    Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
    For correspondence
    a.dady@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Lindsay Davidson

    Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Pamela A Halley

    Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Kate G Storey

    Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
    For correspondence
    k.g.storey@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3506-1287

Funding

Wellcome Trust (WT102817AIA)

  • Kate G Storey

Wellcome Trust (WT102817/Z/13/A)

  • Kate G Storey

Wellcome Trust (WT101468)

  • Kate G Storey

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Ethics

Human subjects: Human embryonic tissue (4 to 6 weeks of gestation) was obtained from the MRC/ Wellcome-Trust (grant no. 006237/1) funded Human Developmental Biology Resource (HDBR; www.hdbr.org) with appropriate maternal written consent and approval from the London Fulham Research Ethics Committee (18/LO/ 0822) and the Newcastle and North Tyneside NHS Health Authority Joint Ethics Committee (08/H0906/21+5). HDBR is regulated by the UK Human Tissue Authority (HTA; www.hta.gov.uk) and operates in accordance with the relevant HTA codes of practice. This work was part of project no. 200407 registered with the HDBR.Human ESC lines H9 and H1 expressing DCXCit/Y were provided by WiCel and all work with hESCs was undertaken in approval of the UK Stem Cell Bank steering committee (license number SCSC14-29).

Version history

  1. Received: February 5, 2021
  2. Preprint posted: February 8, 2021 (view preprint)
  3. Accepted: February 2, 2022
  4. Accepted Manuscript published: February 21, 2022 (version 1)
  5. Version of Record published: March 17, 2022 (version 2)

Copyright

© 2022, Dady et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alwyn Dady
  2. Lindsay Davidson
  3. Pamela A Halley
  4. Kate G Storey
(2022)
Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments
eLife 11:e67283.
https://doi.org/10.7554/eLife.67283

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https://doi.org/10.7554/eLife.67283

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