Spinal cord injury reveals multilineage differentiation of ependymal cells.

Spinal cord injury reveals multilineage differentiation of ependymal cells.
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脊髓损伤揭示了室室室细胞的多链分化。

DOI:
10.1371/journal.pbio.0060182
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发表时间:
2008-07-22
期刊:
影响因子:
9.8
通讯作者:
Frisen, Jonas
Frisen, Jonas
中科院分区:
生物学1区
文献类型:
--
作者:
Meletis, Konstantinos;Barnabe-Heider, Fanie;Carlen, Marie;Evergren, Emma;Tomilin, Nikolay;Shupliakov, Oleg;Frisen, Jonas

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脊髓损伤常导致永久性功能损伤。存在于成人脊髓中的神经干细胞可以在体外扩增,并在移植到受伤脊髓时改善恢复,这表明存在能够促进再生的细胞,但通常不能有效地做到这一点。利用遗传命运图谱,我们发现成人脊髓中几乎所有体外神经干细胞的潜能都存在于中央椎管内的室管膜细胞群中。这些细胞被脊髓损伤招募,不仅产生瘢痕形成的胶质细胞,而且在较小程度上产生少突胶质细胞。调节脊髓损伤后室管膜后代的命运可能为脊髓损伤的细胞替代疗法提供细胞移植的替代方法。全世界每年有3万多人发生脊髓损伤,发病率很高,患者需要长期的身体和医疗护理。最近在成人脊髓中发现的常驻干细胞为药理学操作这些细胞产生促进损伤后恢复的细胞类型开辟了可能性。我们已经使用遗传工具来专门解决被称为室管膜细胞的脊髓亚群的身份和对损伤的反应。这种假定的干细胞群体的遗传标记允许在体外和体内对干细胞活性进行评估。我们发现内衬中央管的室管膜细胞在体外具有神经干细胞的作用,并在体内广泛参与胶质瘢痕的形成。有趣的是,损伤诱导室管膜细胞增殖和室管膜衍生后代向损伤部位迁移。此外,室管膜细胞后代分化并产生星形胶质细胞和髓鞘少突胶质细胞。总之,我们的结果表明室管膜细胞是损伤后非侵入性操作的一个有吸引力的候选群体。脊髓损伤诱导来自室管膜的干细胞向损伤部位迁移的增殖。室管膜细胞的后代分化并产生星形胶质细胞和髓鞘少突胶质细胞。
Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury. Spinal cord injuries occur in more than 30.000 individuals each year worldwide and result in significant morbidity, with patients requiring long physical and medical care. The recent identification of resident stem cells in the adult spinal cord has opened up for the possibility of pharmacological manipulation of these cells to produce cell types promoting recovery after injury. We have employed genetic tools to specifically address the identity and reaction to injury of a spinal cord subpopulation of cells known as ependymal cell. Genetic labeling of this putative stem cell population allows for the evaluation of stem cell activity in vitro and in vivo. We found that ependymal cells lining the central canal act as neural stem cells in vitro and contribute extensively to the glial scar in vivo. Interestingly, injury induces proliferation of ependymal cells and migration of ependyma-derived progeny towards the site of injury. Moreover, ependymal cell progeny differentiate and give rise to astrocytes as well as myelinating oligodendrocytes. In summary, our results point to ependymal cells as an attractive candidate population for non-invasive manipulation after injury. Spinal cord injury induces the proliferation of putative stem cells derived from the ependyma that migrate towards the site of injury. Ependymal cell progeny differentiate and give rise to astrocytes as well as myelinating oligodendrocytes.
DOI: 10.1093/nar/27.22.4324
发表时间: 1999-11-15
影响因子: 14.9
作者:
Indra, AK;Warot, X;Metzger, D
通讯作者: Metzger, D
DOI: 10.1007/bf00690975
发表时间: 1978-01-01
影响因子: 12.7
作者:
BLAKEMORE, WF;PATTERSON, RC
通讯作者: PATTERSON, RC
DOI: 10.1038/37776
发表时间: 1997-12-25
期刊: NATURE
影响因子: 64.8
作者:
Davies, SJA;Fitch, MT;Silver, J
通讯作者: Silver, J
DOI: 10.1038/nature02520
发表时间: 2004-05-06
期刊: NATURE
影响因子: 64.8
作者:
Dor, Y;Brown, J;Melton, DA
通讯作者: Melton, DA