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Directing human neural stem/precursor cells into oligodendrocytes by overexpression of Olig2 transcription factor
Author(s) -
Maire Cécile L.,
Buchet Delphine,
Kerni Christophe,
Deboux Cyrille,
BaronVan Evercooren Anne,
NaitOumesmar Brahim
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22194
Subject(s) - olig2 , biology , demyelinating disorder , neural stem cell , oligodendrocyte , multiple sclerosis , microbiology and biotechnology , myelin , transcription factor , neurosphere , stem cell , precursor cell , in vitro , cellular differentiation , neuroscience , immunology , central nervous system , biochemistry , adult stem cell , gene
Multipotential neural stem/precursor cells of the central nervous system were extensively studied for their properties of generating myelinating oligodendrocytes both in vitro and in vivo upon engraftment in animal models of myelin disorders, such as leucodystrophy and multiple sclerosis. These studies provided proof‐of‐principle that efficient myelination can be achieved by cell transplantation. However, one major drawback of cell‐based therapy of myelin diseases is the difficulty in generating oligodendrocytes efficiently from human fetal neural stem/precursor cells (hNPC). Here we explored whether overexpression of the basic helix‐loop‐helix (bHLH) transcription factor Olig2 in fetal hNPC could enhance the generation of oligodendrocytes both in vitro and in vivo. We report that transduction of hNPC with Olig2‐encoding lentiviral vectors enhances their commitment toward an oligodendroglial fate. Moreover, Olig2‐transduced hNPC, grafted into the dysmyelinated shiverer mouse brain, survived up to 9 weeks, migrated extensively, and differentiated into MBP + myelinating oligodendrocytes. In contrast, control hNPC remained at a less mature stage and generated very few myelinating oligodendrocytes. Our study indicates that bHLH transcription factors, such as Olig2, are interesting targets for directing hNPC into myelinating oligodendrocytes. © 2009 Wiley‐Liss, Inc.