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Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells

Zhang, G-Y; Lv, Z-M; Ma, H-X; Chen, Y; Yuan, Y; Sun, P-X; Feng, Y-Q; ... Li, W; + view all (2022) Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells. Journal of Molecular Cell Biology , 14 (1) , Article mjab076. 10.1093/jmcb/mjab076. Green open access

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Abstract

Spinal cord impairment involving motor neuron degeneration and demyelination can cause life-long disabilities, but effective clinical interventions for restoring neurological functions have yet been developed. In early spinal cord development, neural progenitors in the pMN (‘progenitors of motor neurons’) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on the chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Type: Article
Title: Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jmcb/mjab076
Publisher version: https://doi.org/10.1093/jmcb/mjab076
Language: English
Additional information: Copyright © The Author(s) (2021). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Keywords: human embryonic stem cells, neural differentiation, chemical approach, self-renewing, progenitors of motor neurons, oligodendrocytes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10140216
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