Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human Models

被引:103
作者
Djelloul, Mehdi [1 ,2 ,3 ]
Holmqvist, Staffan [1 ,2 ,3 ]
Boza-Serrano, Antonio [2 ,4 ]
Azevedo, Carla [1 ,2 ,3 ]
Yeung, Maggie S. [5 ]
Goldwurm, Stefano [6 ]
Frisen, Jonas [5 ]
Deierborg, Tomas [2 ,4 ]
Roybon, Laurent [1 ,2 ,3 ]
机构
[1] Lund Univ, Dept Expt Med Sci, Wallenberg Neurosci Ctr, Stem Cell Lab CNS Dis Modeling, S-22184 Lund, Sweden
[2] Lund Univ, Strateg Res Area MultiPark, S-22184 Lund, Sweden
[3] Lund Univ, Lund Stem Cell Ctr, S-22184 Lund, Sweden
[4] Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden
[5] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
[6] Ist Clin Perfezionamento, Parkinson Inst, I-20126 Milan, Italy
关键词
MULTIPLE SYSTEM ATROPHY; MESSENGER-RNA EXPRESSION; PLURIPOTENT STEM-CELLS; PARKINSONS-DISEASE; PROGENITOR CELLS; HUMAN BRAIN; MOUSE MODEL; DEGENERATION; INCLUSIONS; GENERATION;
D O I
10.1016/j.stemcr.2015.07.002
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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 ASYN during oligodendrocyte maturation. Additionally, we show the presence of transcripts in PDGFRA/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.
引用
收藏
页码:174 / 184
页数:11
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