Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo

Sangita Biswas, Seung Hyuk Chung, Peng Jiang, Samaneh Dehghan, Wenbin Deng

Research output: Contribution to journalArticle

Abstract

In this study, we have developed highly expandable neural stem cells (NSCs) from HESCs and iPSCs that artificially express the oligodendrocyte (OL) specific transcription factor gene Zfp488. This is enough to restrict them to an exclusive oligodendrocyte progenitor cell (OPC) fate during differentiation in vitro and in vivo. During CNS development, Zfp488 is induced during the early stages of OL generation, and then again during terminal differentiation of OLs. Interestingly, the human ortholog Znf488, crucial for OL development in human, has been recently identified to function as a dorsoventral pattering regulator in the ventral spinal cord for the generation of P1, P2/pMN, and P2 neural progenitor domains. Forced expression of Zfp488 gene in human NSCs led to the robust generation of OLs and suppression of neuronal and astrocyte fate in vitro and in vivo. Zfp488 expressing NSC derived oligodendrocytes are functional and can myelinate rat dorsal root ganglion neurons in vitro, and form myelin in Shiverer mice brain in vivo. After transplantation near a site of demyelination, Zfp488 expressing hNSCs migrated to the lesion and differentiated into premyelinating OLs. A certain fraction also homed in the subventricular zone (SVZ). Zfp488-ZsGreen1-hNSC derived OLs formed compact myelin in Shiverer mice brain seen under the electron microscope. Transplanted human neural stem cells (NSC) that have the potential to differentiate into functional oligodendrocytes in response to remyelinating signals can be a powerful therapeutic intervention for disorders where oligodendrocyte (OL) replacement is beneficial.

Original languageEnglish (US)
Article number9013
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Neural Stem Cells
Oligodendroglia
Neuroglia
Cell Differentiation
Myelin Sheath
Lateral Ventricles
Brain
Spinal Ganglia
Human Development
Demyelinating Diseases
In Vitro Techniques
Astrocytes
Spinal Cord
Transcription Factors
Stem Cells
Transplantation
Electrons
Gene Expression
Neurons
Genes

ASJC Scopus subject areas

  • General

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Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo. / Biswas, Sangita; Chung, Seung Hyuk; Jiang, Peng; Dehghan, Samaneh; Deng, Wenbin.

In: Scientific reports, Vol. 9, No. 1, 9013, 01.12.2019.

Research output: Contribution to journalArticle

Biswas, Sangita ; Chung, Seung Hyuk ; Jiang, Peng ; Dehghan, Samaneh ; Deng, Wenbin. / Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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