Wind, M. and Tsakiridis, A. orcid.org/0000-0002-2184-2990 (2021) In vitro generation of posterior motor neurons from human pluripotent stem cells. Current Protocols, 1 (9). e244. ISSN 2691-1299
Abstract
The ability to generate spinal cord motor neurons from human pluripotent stem cells (hPSCs) is of great use for modelling motor neuron–based diseases and cell-replacement therapies. A key step in the design of hPSC differentiation strategies aiming to produce motor neurons involves induction of the appropriate anteroposterior (A-P) axial identity, an important factor influencing motor neuron subtype specification, functionality, and disease vulnerability. Most current protocols for induction of motor neurons from hPSCs produce predominantly cells of a mixed hindbrain/cervical axial identity marked by expression of Hox paralogous group (PG) members 1-5, but are inefficient in generating high numbers of more posterior thoracic/lumbosacral Hox PG(8-13)+ spinal cord motor neurons. Here, we describe a protocol for efficient generation of thoracic spinal cord cells and motor neurons from hPSCs. This step-wise protocol relies on the initial generation of a neuromesodermal-potent axial progenitor population, which is differentiated first to produce posterior ventral spinal cord progenitors and subsequently to produce posterior motor neurons exhibiting a predominantly thoracic axial identity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | human pluripotent stem cells (hPSCs); motor neurons; neuromesodermal progenitors |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/P000444/1 EUROPEAN COMMISSION - HORIZON 2020 824070 MEDICAL RESEARCH COUNCIL MR/V002163/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Oct 2021 15:17 |
Last Modified: | 10 Feb 2023 14:11 |
Status: | Published |
Publisher: | Wiley Periodicals LLC |
Refereed: | Yes |
Identification Number: | 10.1002/cpz1.244 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:178907 |