CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells.

CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells.
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DOI:
10.1038/nbt.1972
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发表时间:
2011-09-25
影响因子:
46.9
通讯作者:
--
中科院分区:
工程技术1区
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--
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髓鞘疾病的实验模型可以通过将少突胶质细胞祖细胞(OPCs)移植到受影响的脑或脊髓中来治疗。OPCs表达由MAb A2 B5识别的神经节苷脂,但该标记物也识别谱系限制的星形胶质细胞和未成熟的神经元。为了建立一种更有效的分离髓鞘原性OPCs的方法,我们询问是否可以基于PDGFRα表位CD 140 a的表达,使用FACS从胎儿人前脑中分选PDGFα受体+细胞。CD 140 a+分离株作为有丝分裂双能祖细胞维持,其可被指示为少突胶质细胞或星形胶质细胞的命运。移植的CD 140 a+细胞具有高度迁移性,并迅速和强大的髓鞘化的低髓鞘化颤抖小鼠脑,更有效地比A2 B5分选细胞。CD 140 a+细胞的微阵列分析揭示了它们的CD 9以及PTN-PTPRZ 1、wnt、notch和BMP通路组分的差异表达,表明这些细胞中自我更新和命运限制通路的动态相互作用。
Experimental models of myelin disorders can be treated by the transplantation of oligodendrocyte progenitor cells (OPCs) into the affected brain or spinal cord. OPCs express gangliosides recognized by MAb A2B5, but this marker also identifies lineage-restricted astrocytes and immature neurons. To establish a more efficient means of isolating myelinogenic OPCs, we asked if FACS could be used to sort PDGFα receptor+ cells from fetal human forebrain, based on expression of the PDGFRα epitope CD140a. CD140a+ isolates were maintained as mitotic bipotential progenitors that could be instructed to either oligodendrocyte or astrocyte fate. Transplanted CD140a+ cells were highly migratory, and rapidly and robustly myelinated the hypomyelinated shiverer mouse brain, more efficiently than did A2B5-sorted cells. Microarray analysis of CD140a+ cells revealed their differential expression of CD9, as well as of PTN-PTPRZ1, wnt, notch and BMP pathway components, indicating the dynamic interaction of self-renewal and fate-restricting pathways in these cells.
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