Neural stem cells and oligodendrocyte progenitor cells compete for remyelination in the corpus callosum.
Neural stem cells and oligodendrocyte progenitor cells compete for remyelination in the corpus callosum.
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DOI：
10.3389/fncel.2023.1114781
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发表时间：
2023
影响因子：
5.3
通讯作者：
Salzer, James L. L.
中科院分区：
文献类型：
--
作者：
Moyon, Sarah;Holloman, Mara;Salzer, James L. L.
关键词：
脱髓鞘疾病如多发性硬化症的主要治疗目标是改善髓鞘再生，从而恢复有效的轴突传导并防止神经变性。在成人中枢神经系统（CNS）中，实质少突胶质细胞祖细胞（pOPC）以及在较小程度上预先存在的少突胶质细胞（OL）和由脑室下区（SVZ）中的神经干细胞（NSC）产生的少突胶质细胞能够形成新的髓鞘。由于它们的自我更新能力和它们的后代在CNS内广泛迁移的能力，NSC代表了可以靶向通过pOPC补充修复的髓鞘再生细胞的额外来源。然而，在脱髓鞘疾病和疾病模型中，NSC对髓鞘修复的贡献是适度的，并且在靠近SVZ的区域中最明显。我们假设，神经干细胞衍生的细胞可能会竞争与OPC的髓鞘再生相同的轴突，与pOPC作为主要的髓鞘再生细胞，由于其广泛分布在成人中枢神经系统，从而限制了神经干细胞后代的贡献。在这里，我们已经使用了一个双报告基因，遗传命运定位策略，以表征贡献的pOPCs和神经干细胞衍生的OLs的髓鞘再生后，铜蛋白诱导的脱髓鞘。我们证实，虽然pOPCs是胼胝体中主要的髓鞘再生细胞，但神经干细胞衍生的细胞也被激活并招募到脱髓鞘病变中。基因阻断pOPC分化导致NSC-derived细胞向脱髓鞘胼胝体的募集和向OLs的分化显著增加。这些结果有力地表明，pOPC和NSC后代竞争修复白色物质损伤。他们强调了当pOPC的贡献不足以影响完全髓鞘再生时靶向NSC以改善修复的潜在意义。
A major therapeutic goal in demyelinating diseases, such as Multiple Sclerosis, is to improve remyelination, thereby restoring effective axon conduction and preventing neurodegeneration. In the adult central nervous system (CNS), parenchymal oligodendrocyte progenitor cells (pOPCs) and, to a lesser extent, pre-existing oligodendrocytes (OLs) and oligodendrocytes generated from neural stem cells (NSCs) in the sub-ventricular zone (SVZ) are capable of forming new myelin sheaths. Due to their self-renewal capabilities and the ability of their progeny to migrate widely within the CNS, NSCs represent an additional source of remyelinating cells that may be targeted to supplement repair by pOPCs. However, in demyelinating disorders and disease models, the NSC contribution to myelin repair is modest and most evident in regions close to the SVZ. We hypothesized that NSC-derived cells may compete with OPCs to remyelinate the same axons, with pOPCs serving as the primary remyelinating cells due to their widespread distribution within the adult CNS, thereby limiting the contribution of NSC-progeny. Here, we have used a dual reporter, genetic fate mapping strategy, to characterize the contribution of pOPCs and NSC-derived OLs to remyelination after cuprizone-induced demyelination. We confirmed that, while pOPCs are the main remyelinating cells in the corpus callosum, NSC-derived cells are also activated and recruited to demyelinating lesions. Blocking pOPC differentiation genetically, resulted in a significant increase in the recruitment NSC-derived cells into the demyelinated corpus callosum and their differentiation into OLs. These results strongly suggest that pOPCs and NSC-progeny compete to repair white matter lesions. They underscore the potential significance of targeting NSCs to improve repair when the contribution of pOPCs is insufficient to affect full remyelination.
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影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
DOI：
10.1073/pnas.1808064115
发表时间：
2018-12-11
影响因子：
11.1
作者：
Duncan, Ian D.;Radcliff, Abigail B.;Wierenga, Lauren A.
通讯作者：
Wierenga, Lauren A.
影响因子：
4.7
作者：
Loulier, Karine;Ruat, Martial;Traiffort, Elisabeth
通讯作者：
Traiffort, Elisabeth
影响因子：
12.7
作者：
Boyd A;Zhang H;Williams A
通讯作者：
Williams A
炎症脱髓鞘过程中加速髓鞘再生可防止轴突损失并改善功能恢复
影响因子：
7.7
作者：
Mei, Feng;Lehmann-Horn, Klaus;Chan, Jonah R.
通讯作者：
Chan, Jonah R.