Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion

Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion
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DOI:
10.1002/jnr.10338
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发表时间:
2002-09-15
影响因子:
4.2
通讯作者:
Nishiyama, A
Nishiyama, A
中科院分区:
医学3区
文献类型:
--
作者:
Watanabe, M;Toyama, Y;Nishiyama, A

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表达NG 2蛋白聚糖的细胞(NG 2+细胞)构成成年哺乳动物中枢神经系统(CNS)中的大量细胞群。它们在培养物中产生成熟的少突胶质细胞,因此被认为是少突胶质细胞祖细胞(OPC)。它们在对CNS的各种损伤的反应中增殖,但它们在体内分化成少突胶质细胞的能力尚未建立。我们用溴脱氧尿苷(BrdU)追踪NG 2+细胞的命运,这些细胞在成年大鼠脊髓中对化学诱导的髓鞘形成病变作出反应而增殖。通过单次注射BrdU标记损伤后24小时增殖的细胞,并在损伤后28天(28 dpl)的不同时间检查其抗原表型。最初,在2dpl,NG 2 +/BrdU+细胞几乎只在病变的周边被发现。伤后7 d,NG 2 +/BrdU+细胞在损伤中心区增多,周围区减少。病变内NG 2 +/BrdU+细胞的数量随着时间的推移进一步减少,伴随着髓鞘再生的进展和BrdU+成熟少突胶质细胞的出现。H-3-TdR和BrdU双标记结合NG 2免疫组化显示,病变中部分NG 2+细胞至少经历了两轮细胞分裂。这些观察结果有力地表明,NG 2 +/BrdU+细胞,出现在响应于clemyelinating损伤引起成熟的髓鞘再生少突胶质细胞,提供了在体内的证据,NG 2+细胞分化成少突胶质细胞。(C)2002 Wiley-Liss,Inc.
Cells that express the NG2 proteoglycan (NG2+ cells) constitute a large cell population in the adult mammalian central nervous system (CNS). They give rise to mature oligodendrocytes in culture and are thus considered to be oligodendrocyte progenitor cells (OPCs). They proliferate in response to a variety of insults to the CNS, but their ability to differentiate into oligodendrocytes in vivo has not been established. We used bromodeoxyuridine (BrdU) to trace the fate of NG2+ cells that proliferated in response to a chemically induced clemyelinating lesion in the adult rat spinal cord. Cells that were proliferating 24 hr after lesioning were labeled by a single injection of BrdU, and their antigenic phenotype was examined at various times up to 28 days post-lesioning (28 dpl). Initially, at 2 dpl, NG2+/BrdU+ cells were found almost exclusively at the periphery of the lesion. At 7 dpl, the number of NG2+/BrdU+ cells increased in the lesion center and decreased from the surrounding areas. The number of NG2+/BrdU+ cells inside the lesion further decreased with time, concomitant with progression of remyelination and appearance of BrdU+ mature oligodendrocytes. Double labeling with H-3-thymidine and BrdU combined with NG2 immunohistochemistry showed that some NG2+ cells in the lesion had undergone at least two rounds of cell division. These observations strongly suggest that NG2+/BrdU+ cells that appeared in response to the clemyelinating insult gave rise to mature remyelinating oligodendrocytes, providing an in vivo evidence for the differentiation of NG2+ cells into oligodendrocytes. (C) 2002 Wiley-Liss, Inc.