Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human Models.
Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human Models.
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DOI：
10.1016/j.stemcr.2015.07.002
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发表时间：
2015-08-11
影响因子：
5.9
通讯作者：
Roybon L
中科院分区：
文献类型：
--
作者：
Djelloul M;Holmqvist S;Boza-Serrano A;Azevedo C;Yeung MS;Goldwurm S;Frisén J;Deierborg T;Roybon L
在这项研究中，我们寻找证据的α-突触核蛋白（ASYN）的表达在少突胶质细胞，作为一个可能的内源性来源的ASYN解释其存在于胶质细胞中发现的多系统萎缩（MSA）和帕金森病（PD）。我们在从啮齿动物脑中分离的少突胶质细胞谱系祖细胞、从胚胎干细胞产生的少突胶质细胞以及从健康个体和诊断患有MSA或PD的患者的成纤维细胞产生的诱导多能干细胞中鉴定了ASYN。值得注意的是，我们观察到在少突胶质细胞成熟过程中ASYN显著减少。此外，我们显示了分别从啮齿动物和人健康和患病脑中通过FACS分离的PDGFR A/CD 140 a+细胞和SOX 10+少突胶质细胞谱系核中存在转录物。我们的工作确定ASYN在少突胶质细胞谱系细胞，它提供了额外的体外细胞模型，应该提供重要的见解ASYN在少突胶质细胞发育和疾病的功能意义。ASYN在少突胶质细胞发育过程中表达ASYN表达早在PDGFRA+少突胶质细胞谱系阶段就开始，在来自人脑的少突胶质细胞谱系细胞中鉴定出SNCA转录物。人iPSC提供了用于研究少突胶质细胞中ASYN的细胞模型。在这篇文章中，罗伊邦和他的同事表明，少突胶质细胞在发育过程中表达编码ASYN的SNCA基因。他们的工作为进一步理解ASYN在少突胶质细胞发育和疾病中的功能意义奠定了坚实的基础，并为突触核蛋白病建模提供了细胞模型。
In this study, we sought evidence for alpha-synuclein (ASYN) expression in oligodendrocytes, as a possible endogenous source of ASYN to explain its presence in glial inclusions found in multiple system atrophy (MSA) and Parkinson’s disease (PD). We identified ASYN in oligodendrocyte lineage progenitors isolated from the rodent brain, in oligodendrocytes generated from embryonic stem cells, and in induced pluripotent stem cells produced from fibroblasts of a healthy individual and patients diagnosed with MSA or PD, in cultures in vitro. Notably, we observed a significant decrease in ΑSYN during oligodendrocyte maturation. Additionally, we show the presence of transcripts in PDGFRΑ/CD140a+ cells and SOX10+ oligodendrocyte lineage nuclei isolated by FACS from rodent and human healthy and diseased brains, respectively. Our work identifies ASYN in oligodendrocyte lineage cells, and it offers additional in vitro cellular models that should provide significant insights of the functional implication of ASYN during oligodendrocyte development and disease. ASYN is expressed during oligodendrocyte development ASYN expression begins as early as PDGFRA+ oligodendrocyte lineage stage SNCA transcripts are identified in oligodendrocyte lineage cells from the human brain Human iPSCs provide cellular models for studying ASYN in oligodendrocytes The origin of ASYN present in glial inclusions in synucleinopathies is still elusive. In this article, Roybon and colleagues show that oligodendrocytes express the SNCA gene encoding for ASYN during their development. Their work establishes a strong basis for further understanding the functional implication of ASYN during oligodendrocyte development and disease, and it offers cellular models for modeling synucleionopathies.