| 1. |
- Shinjyo, Noriko, et al.
(författare)
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Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells.
- 2009
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 27:11, s. 2824-32
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Tidskriftsartikel (refereegranskat)abstract
- Anaphylatoxin C3a is a third complement component (C3)-derived peptide, the multiple functions of which range from stimulation of inflammation to neuroprotection. In a previous study, we have shown that signaling through C3a receptor positively regulates in vivo neurogenesis in adult mouse brain. Here, we studied the direct effects of C3a on adult mouse whole brain-derived neural progenitor cells (NPCs) in vitro. Our results demonstrate that NPCs bind C3a in a specific and reversible manner and that C3a stimulates neuronal differentiation of NPCs. Furthermore, C3a stimulated the migration of NPCs induced by low concentrations of stromal cell-derived factor (SDF)-1alpha, whereas it inhibited NPC migration at high concentration of SDF-1alpha. In the same manner, C3a modulated SDF-1alpha-induced extracellular-signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in these cells. In addition, C3a had inhibitory effect on SDF-1alpha-induced neuronal differentiation of NPCs. These data show that C3a modulates SDF-1alpha-induced differentiation and migration of these cells, conceivably through the regulation of ERK1/2 phosphorylation. Our results provide the first evidence that C3a regulates neurogenesis by directly affecting the fate and properties of NPCs.
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| 2. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
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Astrocytes negatively regulate neurogenesis through the Jagged1-mediated notch pathway.
- 2012
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 30:10, s. 2320-9
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis is regulated by a number of cellular players within the neurogenic niche. Astrocytes participate actively in brain development, regulation of the mature central nervous system (CNS), and brain plasticity. They are important regulators of the local environment in adult neurogenic niches through the secretion of diffusible morphogenic factors, such as Wnts. Astrocytes control the neurogenic niche also through membrane-associated factors, however, the identity of these factors and the mechanisms involved are largely unknown. In this study, we sought to determine the mechanisms underlying our earlier finding of increased neuronal differentiation of neural progenitor cells when cocultured with astrocytes lacking glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-) Vim(-/-) ). We used primary astrocyte and neurosphere cocultures to demonstrate that astrocytes inhibit neuronal differentiation through a cell-cell contact. GFAP(-/-) Vim(-/-) astrocytes showed reduced endocytosis of Notch ligand Jagged1, reduced Notch signaling, and increased neuronal differentiation of neurosphere cultures. This effect of GFAP(-/-) Vim(-/-) astrocytes was abrogated in the presence of immobilized Jagged1 in a manner dependent on the activity of γ-secretase. Finally, we used GFAP(-/-) Vim(-/-) mice to show that in the absence of GFAP and vimentin, hippocampal neurogenesis under basal conditions as well as after injury is increased. We conclude that astrocytes negatively regulate neurogenesis through the Notch pathway, and endocytosis of Notch ligand Jagged1 in astrocytes and Notch signaling from astrocytes to neural stem/progenitor cells depends on the intermediate filament proteins GFAP and vimentin.
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