Oligodendrocyte differentiation from human neural stem cells: A novel role for c-Src

Le Wang, Caitlin R. Schlagal, Junling Gao, Yan Hao, Tiffany J. Dunn, Erica L. McGrath, Javier Allende Labastida, Yongjia Yu, Shi qing Feng, Shao yu Liu, Ping Wu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Human neural stem cells (hNSCs) can differentiate into an oligodendrocyte lineage to facilitate remyelination in patients. Molecular mechanisms underlying oligodendrocyte fate specification remains unknown, hindering the development of efficient methods to generate oligodendrocytes from hNSCs. We have found that Neurobasal-A medium (NB) is capable of inducing hNSCs to oligodendrocyte progenitor cells (OPCs). We identified several signaling molecules are altered after cultivation in NB medium, including Akt, ERK1/2 and c-Src. While sustained activation of Akt and ERK1/2 during both NB induction and subsequent differentiation was required for OPC differentiation, c-Src phosphorylation was increased temporally during the period of NB induction. Both pharmacological inhibition and RNA interference confirmed that a transient elevation of phospho-c-Src is critical for OPC induction. Furthermore, inactivation of c-Src inhibited phosphorylation of Akt and ERK1/2. In summary, we identified a novel and critical role of c-Src in guiding hNSC differentiation to an oligodendrocyte lineage.

Original languageEnglish (US)
Pages (from-to)21-32
Number of pages12
JournalNeurochemistry International
Volume120
DOIs
StatePublished - Nov 1 2018

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Neural Stem Cells
Oligodendroglia
Stem Cells
Cell Differentiation
Phosphorylation
RNA Interference
Pharmacology

Keywords

  • Differentiation
  • Human neural stem cells
  • Oligodendrocyte precursor cells
  • Remyelination
  • Src family kinases

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Oligodendrocyte differentiation from human neural stem cells : A novel role for c-Src. / Wang, Le; Schlagal, Caitlin R.; Gao, Junling; Hao, Yan; Dunn, Tiffany J.; McGrath, Erica L.; Labastida, Javier Allende; Yu, Yongjia; Feng, Shi qing; Liu, Shao yu; Wu, Ping.

In: Neurochemistry International, Vol. 120, 01.11.2018, p. 21-32.

Research output: Contribution to journalArticle

Wang, L, Schlagal, CR, Gao, J, Hao, Y, Dunn, TJ, McGrath, EL, Labastida, JA, Yu, Y, Feng, SQ, Liu, SY & Wu, P 2018, 'Oligodendrocyte differentiation from human neural stem cells: A novel role for c-Src', Neurochemistry International, vol. 120, pp. 21-32. https://doi.org/10.1016/j.neuint.2018.07.006
Wang, Le ; Schlagal, Caitlin R. ; Gao, Junling ; Hao, Yan ; Dunn, Tiffany J. ; McGrath, Erica L. ; Labastida, Javier Allende ; Yu, Yongjia ; Feng, Shi qing ; Liu, Shao yu ; Wu, Ping. / Oligodendrocyte differentiation from human neural stem cells : A novel role for c-Src. In: Neurochemistry International. 2018 ; Vol. 120. pp. 21-32.
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AU - Dunn, Tiffany J.

AU - McGrath, Erica L.

AU - Labastida, Javier Allende

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AU - Feng, Shi qing

AU - Liu, Shao yu

AU - Wu, Ping

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AB - Human neural stem cells (hNSCs) can differentiate into an oligodendrocyte lineage to facilitate remyelination in patients. Molecular mechanisms underlying oligodendrocyte fate specification remains unknown, hindering the development of efficient methods to generate oligodendrocytes from hNSCs. We have found that Neurobasal-A medium (NB) is capable of inducing hNSCs to oligodendrocyte progenitor cells (OPCs). We identified several signaling molecules are altered after cultivation in NB medium, including Akt, ERK1/2 and c-Src. While sustained activation of Akt and ERK1/2 during both NB induction and subsequent differentiation was required for OPC differentiation, c-Src phosphorylation was increased temporally during the period of NB induction. Both pharmacological inhibition and RNA interference confirmed that a transient elevation of phospho-c-Src is critical for OPC induction. Furthermore, inactivation of c-Src inhibited phosphorylation of Akt and ERK1/2. In summary, we identified a novel and critical role of c-Src in guiding hNSC differentiation to an oligodendrocyte lineage.

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