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Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor.

Lee H, Bae JS, Jin HK - Mol. Cells (2015)

Bottom Line: We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation.Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs.Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Neuroplasticity Research Group, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.

ABSTRACT
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

No MeSH data available.


Related in: MedlinePlus

Deletion of Gba results in a severe enzyme deficiency and accumulation of GluCer in the NSCs. (A) GCase activity was reduced to a greater degree in NSCs of Gba−/− mice compared with that in NSCs of Gba+/− mice (n = 5 per group). (B) GluCer accumulated in NSCs from Gba−/− mice (n = 5 per group). All data are presented as the mean ± SEM. *p < 0.05 compared with the Gba+/− controls.
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f1-molce-38-9-806: Deletion of Gba results in a severe enzyme deficiency and accumulation of GluCer in the NSCs. (A) GCase activity was reduced to a greater degree in NSCs of Gba−/− mice compared with that in NSCs of Gba+/− mice (n = 5 per group). (B) GluCer accumulated in NSCs from Gba−/− mice (n = 5 per group). All data are presented as the mean ± SEM. *p < 0.05 compared with the Gba+/− controls.

Mentions: To confirm that nestin-Cre-mediated deletion of the GCase gene disrupted GCase activity, NSCs were obtained from Gba+/− and Gba−/− mice. NSCs isolated from the cortex of Gba−/− neonatal mouse exhibited reduced GCase activity (Fig. 1A), and higher levels of GluCer compared with that in control NSCs (Fig. 1B).


Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor.

Lee H, Bae JS, Jin HK - Mol. Cells (2015)

Deletion of Gba results in a severe enzyme deficiency and accumulation of GluCer in the NSCs. (A) GCase activity was reduced to a greater degree in NSCs of Gba−/− mice compared with that in NSCs of Gba+/− mice (n = 5 per group). (B) GluCer accumulated in NSCs from Gba−/− mice (n = 5 per group). All data are presented as the mean ± SEM. *p < 0.05 compared with the Gba+/− controls.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588724&req=5

f1-molce-38-9-806: Deletion of Gba results in a severe enzyme deficiency and accumulation of GluCer in the NSCs. (A) GCase activity was reduced to a greater degree in NSCs of Gba−/− mice compared with that in NSCs of Gba+/− mice (n = 5 per group). (B) GluCer accumulated in NSCs from Gba−/− mice (n = 5 per group). All data are presented as the mean ± SEM. *p < 0.05 compared with the Gba+/− controls.
Mentions: To confirm that nestin-Cre-mediated deletion of the GCase gene disrupted GCase activity, NSCs were obtained from Gba+/− and Gba−/− mice. NSCs isolated from the cortex of Gba−/− neonatal mouse exhibited reduced GCase activity (Fig. 1A), and higher levels of GluCer compared with that in control NSCs (Fig. 1B).

Bottom Line: We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation.Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs.Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Neuroplasticity Research Group, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.

ABSTRACT
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

No MeSH data available.


Related in: MedlinePlus