| Autor: |
Weifeng Li, Cynthia Berlinicke, Yinyin Huang, Stefanie Giera, Anna G. McGrath, Weixiang Fang, Chaoran Chen, Felipe Takaesu, Xiaoli Chang, Yukan Duan, Dinesh Kumar, Calvin Chang, Hai-Quan Mao, Guoqing Sheng, James C. Dodge, Hongkai Ji, Stephen Madden, Donald J. Zack, Xitiz Chamling |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 26, Iss 3, Pp 106156- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2023.106156 |
| Popis: |
Summary: Promoting myelination capacity of endogenous oligodendrocyte precursor cells (OPCs) is a promising therapeutic approach for CNS demyelinating disorders such as Multiple Sclerosis (MS). To aid in the discovery of myelination-promoting compounds, we generated a genome-engineered human pluripotent stem cell (hPSC) line that consists of three reporters: identification-and-purification tag, GFP, and secreted-NanoLuc, driven by the endogenous PDGFRA, PLP1, and MBP genes, respectively. Using this cell line, we established a high-throughput drug screening platform and performed a small-molecule screen, which identified at least two myelination-promoting small-molecule (Ro1138452 and SR2211) that target prostacyclin (IP) receptor and retinoic acid receptor-related orphan receptor γ (RORγ), respectively. Single-cell-transcriptomic analysis of differentiating OPCs treated with these molecules further confirmed that they promote oligodendrocyte differentiation and revealed several pathways that are potentially modulated by them. The molecules and their target pathways provide promising targets for the possible development of remyelination-based therapy for MS and other demyelinating disorders. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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