Wind, M., Gogolou, A. orcid.org/0000-0002-3581-2426, Manipur, I. et al. (8 more authors) (2021) Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives. Development, 148 (6). dev194415. ISSN 0950-1991
Abstract
The anteroposterior axial identity of motor neurons (MNs) determines their functionality and vulnerability to neurodegeneration. Thus, it is a crucial parameter in the design of strategies aiming to produce MNs from human pluripotent stem cells (hPSCs) for regenerative medicine/disease modelling applications. However, the in vitro generation of posterior MNs corresponding to the thoracic/lumbosacral spinal cord has been challenging. Although the induction of cells resembling neuromesodermal progenitors (NMPs), the bona fide precursors of the spinal cord, offers a promising solution, the progressive specification of posterior MNs from these cells is not well defined. Here, we determine the signals guiding the transition of human NMP-like cells toward thoracic ventral spinal cord neurectoderm. We show that combined WNT-FGF activities drive a posterior dorsal pre-/early neural state, whereas suppression of TGFβ-BMP signalling pathways promotes a ventral identity and neural commitment. Based on these results, we define an optimised protocol for the generation of thoracic MNs that can efficiently integrate within the neural tube of chick embryos. We expect that our findings will facilitate the comparison of hPSC-derived spinal cord cells of distinct axial identities.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Neuromesodermal progenitors; Human pluripotent stem cells; In vitro differentiation; Motor neurons; Regional identity; Spinal cord |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number Biotechnology and Biological Sciences Research Council BB/P000444/1 European Commission - Horizon 2020 824070 The Wellcome Trust 212247/Z/18/Z Medical Research Council MR/M010864/1; MR/V002163/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Aug 2021 06:49 |
Last Modified: | 23 Sep 2021 00:39 |
Status: | Published |
Publisher: | The Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/dev.194415 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:177076 |