Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.
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CNS再髓时,周细胞刺激少突胶质细胞祖细胞分化。

DOI:
10.1016/j.celrep.2017.08.007
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发表时间:
2017-08-22
期刊:
影响因子:
8.8
通讯作者:
Rivera FJ
Rivera FJ
中科院分区:
生物学1区
文献类型:
--
作者:
De La Fuente AG;Lange S;Silva ME;Gonzalez GA;Tempfer H;van Wijngaarden P;Zhao C;Di Canio L;Trost A;Bieler L;Zaunmair P;Rotheneichner P;O'Sullivan A;Couillard-Despres S;Errea O;Mäe MA;Andrae J;He L;Keller A;Bátiz LF;Betsholtz C;Aigner L;Franklin RJM;Rivera FJ

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神经血管生态位在中枢神经系统髓鞘再生中的作用尚不完全清楚。本研究表明,脱髓鞘后,cns驻留周细胞(PCs)增殖,实质非血管相关pc样细胞(plc)迅速发育。在髓鞘再生过程中,成熟的少突胶质细胞靠近pc。在Pdgfbret/ret小鼠中,PC数量减少,少突胶质细胞祖细胞(OPC)分化延迟,尽管髓鞘再生继续完成。在离体小脑脱髓鞘切片模型中,pc条件培养基加速和增强了OPC体外分化,并增加了脱髓鞘的再脱髓鞘率。我们发现Lama2是一种pc衍生因子,可促进OPC分化。因此,PCs的功能作用不仅限于血管稳态,还包括参与再生的成人中枢神经系统祖细胞的调节。CNS-resident PCs对脱髓鞘有反应,并被发现接近于分化的OPC PC-deficient小鼠在CNS髓鞘再生过程中显示延迟的OPC分化pc条件培养基加速OPC分化并增强髓鞘再生pc来源的LAMA2诱导OPC分化在毒素诱导的PC-deficient小鼠脱髓鞘后,通过多种体外方法,Guzman dela Fuente等人发现CNS周细胞(PCs)对脱髓鞘有反应,并且通过LAMA2的分泌,在髓鞘再生过程中刺激少突胶质祖细胞分化。这些发现将PC功能从血管稳态扩展到再生。
The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration. CNS-resident PCs react to demyelination and are found close to differentiating OPCs PC-deficient mice show delayed OPC differentiation during CNS remyelination PC-conditioned medium accelerates OPC differentiation and enhances remyelination PC-derived LAMA2 induces OPC differentiation Following toxin-induced demyelination in PC-deficient mice and using a number of in vitro approaches, Guzman de la Fuente et al. show that CNS pericytes (PCs) respond to demyelination and, through Lama2 secretion, stimulate oligodendrocyte progenitor cell differentiation during remyelination. These findings extend PC function beyond vascular homeostasis toward regeneration.
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