Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells
Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells
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DOI：
10.3389/fncel.2019.00085
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发表时间：
2019-03-27
影响因子：
5.3
通讯作者：
Rivera, Francisco J.
中科院分区：
文献类型：
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作者：
Elena Silva, Maria;Lange, Simona;Rivera, Francisco J.
多发性硬化症（MS）是一种中枢神经系统（CNS）的炎症性脱髓鞘疾病。脱髓鞘后，少突胶质细胞祖细胞（OPCs）被激活，它们增殖、迁移并分化为产生髓磷脂的少突胶质细胞。除OPCs外，神经干细胞（NSCs）也可能响应脱髓鞘并产生少突胶质细胞。我们最近的研究表明，中枢神经系统内的周细胞（PCs）对脱髓鞘有反应，增殖并分泌层粘胶蛋白α 2 (Lama2)，这反过来又增强了OPC分化。在这里，我们的目的是评估PCs是否影响体外NSCs的命运选择，以产生新的髓磷脂细胞。事实上，在暴露于pc （PC-CM）衍生的条件培养基后，大多数NSCs产生了表达GalC和髓鞘碱性蛋白（MBP）的少突胶质细胞，而gmap阳性星形胶质细胞的产生则为代价。与这些发现一致，PC-CM诱导少突胶质细胞命运决定因子Olig2的表达增加，而星形胶质细胞决定因子ID2的表达水平降低。最后，用抗lama2抗体对PC-CM进行预孵育，可阻止少突胶质细胞的产生。我们的研究结果表明，pc衍生的Lama2指示NSCs在体外以星形胶质细胞为代价，选择有利于产生髓磷脂细胞的少突胶质细胞的命运。进一步的研究旨在揭示pc在髓鞘再生过程中的作用，可能为开发治疗多发性硬化症的新疗法铺平道路。
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Upon demyelination, oligodendrocyte progenitor cells (OPCs) are activated and they proliferate, migrate and differentiate into myelin-producing oligodendrocytes. Besides OPCs, neural stem cells (NSCs) may respond to demyelination and generate oligodendrocytes. We have recently shown that CNS-resident pericytes (PCs) respond to demyelination, proliferate and secrete Laminin alpha2 (Lama2) that, in turn, enhances OPC differentiation. Here, we aimed to evaluate whether PCs influence the fate choice of NSCs in vitro, towards the production of new myelin-producing cells. Indeed, upon exposure to conditioned medium derived from PCs (PC-CM), the majority of NSCs gave rise to GalC- and myelin basic protein (MBP)-expressing oligodendrocytes at the expense of the generation of GFAP-positive astrocytes. Consistent with these findings, PC-CM induces an increase in the expression of the oligodendrocyte fate determinant Olig2, while the expression level of the astrocyte determinant ID2 is decreased. Finally, pre-incubation of PC-CM with an anti-Lama2 antibody prevented the generation of oligodendrocytes. Our findings indicate that PCs-derived Lama2 instructs NSCs to an oligodendrocyte fate choice favoring the generation of myelin-producing cells at the expense of astrocytes in vitro. Further studies aiming to reveal the role of PCs during remyelination may pave the way for the development of new therapies for the treatment of MS.