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果蝇神经系统中的干细胞衰老与可塑性

Stem cell aging and plasticity in the Drosophila nervous system.

作者信息

Flici Hakima, Giangrande Angela

机构信息

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France.

出版信息

Fly (Austin). 2012 Apr-Jun;6(2):108-12. doi: 10.4161/fly.19797. Epub 2012 Apr 1.

Abstract

The majority of neural stem cells (NSCs) are considered as very plastic precursors that, in vitro, can divide indefinitely or differentiate into neurons or glia under specific conditions. However, in vivo, these cells actively proliferate during development, and later enter quiescence or apoptosis. This raises the issue as to whether stem cells keep their plastic behavior throughout their life, which may impact their therapeutic potential in regenerative medicine. Using the Gcm/Glide (for Glial cell missing/Glial cell deficient) transcription factor, which is able to trigger a complete and stable fate conversion into glia when ectopically expressed, we recently reported that the plasticity of Drosophila NSCs, commonly called neuroblasts (NBs), is age-dependent. When challenged with Gcm/Glide, newborn NBs are more easily converted into glia than old ones. Furthermore, the few old NBs that can be converted frequently generate cells with a stable (NB/glia) intermediate identity, a phenotype characteristic of cancer cells. We here discuss the concept of aging in NSC fate conversion and speculate on how our findings impact the ongoing debate concerning NSC plasticity.

摘要

大多数神经干细胞(NSCs)被认为是极具可塑性的前体细胞,在体外,它们能够无限增殖,或者在特定条件下分化为神经元或神经胶质细胞。然而,在体内,这些细胞在发育过程中会积极增殖,随后进入静止状态或发生凋亡。这就引发了一个问题,即干细胞在其整个生命周期中是否都保持其可塑性,这可能会影响它们在再生医学中的治疗潜力。利用胶质细胞缺失/胶质细胞缺陷(Gcm/Glide)转录因子,当异位表达时,它能够触发完全且稳定的向神经胶质细胞的命运转变,我们最近报道了果蝇神经干细胞(通常称为神经母细胞,NBs)的可塑性是年龄依赖性的。当受到Gcm/Glide的作用时,新生神经母细胞比老龄神经母细胞更容易转变为神经胶质细胞。此外,少数能够被转变的老龄神经母细胞经常产生具有稳定(神经母细胞/神经胶质细胞)中间身份的细胞,这是癌细胞的一种表型特征。我们在此讨论神经干细胞命运转变中的衰老概念,并推测我们的发现如何影响正在进行的关于神经干细胞可塑性的争论。

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