Olig2-expressing progenitor cells preferentially differentiate into oligodendrocytes in cuprizone-induced demyelinated lesions

Islam, Mohammad Shyful; Tatsumi, Kouko; Okuda, Hiromichi; Shiosaka, Sadao; Wanaka, Akio

doi:10.1016/j.neuint.2008.10.011

Cited by 51 publications

(41 citation statements)

References 45 publications

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“…This result was consistent with recent reports that show overexpression of Olig2 transcription factor is sufficient to activate cellular machinery in NSCs, which promotes differentiation into OLs [27,28,[54][55][56]. In addition, although Olig2-overexpressing NSCs differentiated into OLs in NSC differentiation medium, the cells maintained an undifferentiated state in growth medium containing EGF and bFGF.…”

Section: Discussionsupporting

confidence: 93%

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Shen

Wang

et al. 2012

Neurotherapeutics

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Neural stem cell (NSC) transplantation is a major focus of current research for treatment of spinal cord injury (SCI). However, it is very important to promote the survival and differentiation of NSCs into myelinating oligodendrocytes (OLs). In this study, myelin basic protein-activated T (MBP-T) cells were passively immunized to improve the SCI microenvironment. Olig2-overexpressing NSCs were infected with a lentivirus carrying the enhanced green fluorescent protein (GFP) reporter gene to generate Olig2-GFP-NSCs that were transplanted into the injured site to differentiate into OLs. Transferred MBP-T cells infiltrated the injured spinal cord, produced neurotrophic factors, and induced the differentiation of resident microglia and/or infiltrating blood monocytes into an "alternatively activated" anti-inflammatory macrophage phenotype by producing interleukin-13. As a result, the survival of transplanted NSCs increased fivefold in MBP-T cell-transferred rats compared with that of the vehicle-treated control. In addition, the differentiation of MBP-positive OLs increased 12-fold in Olig2-GFP-NSC-transplanted rats compared with that of GFP-NSC-transplanted controls. In the MBP-T cell and Olig2-GFP-NSC combined group, the number of OL-remyelinated axons significantly increased compared with those of all other groups. However, a significant decrease in spinal cord lesion volume and an increase in spared myelin and behavioral recovery were observed in Olig2-NSC-and NSC-transplanted MBP-T cell groups. Collectively, these results suggest that MBP-T cell adoptive immunotherapy combined with NSC transplantation has a synergistic effect on histological and behavioral improvement after traumatic SCI. Although Olig2 overexpression enhances OL differentiation and myelination, the effect on functional recovery may be surpassed by MBP-T cells.

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Section: Discussionsupporting

confidence: 93%

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Shen

Wang

et al. 2012

Neurotherapeutics

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“…10a). This was also confirmed in another recent study where double transgenic mice (8-10 weeks old) which express tamoxifen-inducible Cre-ER under the control of Olig2 promoter and a ROSA-EGFP reporter to trace the fate of Olig2?ve cells showed significant increases in NG2?ve/APC?ve OLs after cuprizone treatment (Islam et al 2009). However, the absence of a cuprizone-induced increase in the density of PDGFaR?ve/GFAP-ve progenitor cells in mice older than 2 months of age would certainly impede the ability of the tissue to generate sufficient numbers of OLs for remyelinating axons in the rostral CC.…”

Section: Discussionsupporting

confidence: 74%

“…A recent report (Islam et al 2009) showed no increase in the percentage of GFAP?ve/GFP?ve cells in the external capsule of 8-10 week-old mice treated with cuprizone and our data also do not show a change in the Olig2 Cyto -ve/ GFAP?ve mature astrocytes in the 2-month cuprizone mice. In this study, we quantified the numbers of cells at three different stages of the astrocyte cell lineage.…”

Section: Discussionsupporting

confidence: 62%

Age-Related and Cuprizone-Induced Changes in Myelin and Transcription Factor Gene Expression and in Oligodendrocyte Cell Densities in the Rostral Corpus Callosum of Mice

2010

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During aging, there is a decrease both in the stability of central nervous system (CNS) myelin once formed and in the efficiency of its repair by oligodendrocytes (OLs). To study CNS remyelination during aging, we used the cuprizone (a copper chelator) mouse model. Inclusion of cuprizone in the diet kills mature OLs and demyelinates axons in the rostral corpus callosum (CC) of mice, which enabled us to characterize age-related changes (i.e., 2-16 months of age) in glial cell response during the recruitment (i.e., demyelination) and differentiation (i.e., remyelination) phases of myelin repair. We have found that the time between 12 and 16 months of age is a critical period during which there is an age-related decrease in the number of OL lineage cells (Olig2(Nuc)+ve/GFAP-ve cells) in the rostral CC of both control mice and mice recovering from cuprizone-induced demyelination. Our results also show there was an age-related impaired recruitment of progenitor cells to replace lost OLs in spite of there being no major age-related decrease in the size of the progenitor cell pool (PDGFalphaR+ve/GFAP-ve, and Olig2(Nuc) +ve/PDGFalphaR+ve cells). However, there were cuprizone-induced increased numbers of astrocyte progenitor cells (Olig2(Cyto)+ve/PDGFalphaR+ve) in these same mice; thus PDGFalphaR+ve progenitor cells in mice as old as 16 months of age retain the ability to differentiate into astrocytes, with this fate choice occurring following cytoplasmic translocation of Olig2. These data reveal for the first time age-related differences in the differentiation of PDGFalphaR+ve progenitor cells into OLs and astrocytes and lead us to suggest that during aging there must be a transcriptional switch mechanism in the progenitor cell fate choice in favor of astrocytes. This may at least partially explain the age-related decrease in efficiency of OL myelination and remyelination.

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“…OPCs can differentiate into OLs in a suitable microenvironment in the spinal cord (Islam et al, 2009). Our previous study and other studies have shown that remyelination could be improved by OFS after SCI in rats (Zhang et al, 2014).…”

Section: Introductionmentioning

confidence: 83%

Improved differentiation of oligodendrocyte precursor cells and neurological function after spinal cord injury in rats by oscillating field stimulation

et al. 2015

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Olig2-expressing progenitor cells preferentially differentiate into oligodendrocytes in cuprizone-induced demyelinated lesions

Cited by 51 publications

References 45 publications

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Effects of Olig2-Overexpressing Neural Stem Cells and Myelin Basic Protein-Activated T Cells on Recovery from Spinal Cord Injury

Age-Related and Cuprizone-Induced Changes in Myelin and Transcription Factor Gene Expression and in Oligodendrocyte Cell Densities in the Rostral Corpus Callosum of Mice

Improved differentiation of oligodendrocyte precursor cells and neurological function after spinal cord injury in rats by oscillating field stimulation

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