生物
干细胞
SOX2
多发性硬化
类有机物
诱导多能干细胞
细胞分化
干细胞标记物
少突胶质细胞
神经干细胞
免疫学
神经科学
细胞生物学
中枢神经系统
髓鞘
遗传学
基因
胚胎干细胞
作者
Nicolas Daviaud,Eric Chen,Tara Edwards,Saud Sadiq
出处
期刊:Biology Open
[The Company of Biologists]
日期:2023-03-06
卷期号:12 (3)
被引量:3
摘要
Multiple sclerosis (MS) is an auto-immune inflammatory disorder affecting the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are implicated in the pathogenesis. We derived cerebral organoids from induced pluripotent stem cells (iPSC) of healthy control subjects as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing remitting MS (RRMS) patients to better understand the pathologic basis of the varied clinical phenotypic expressions of MS. In MS organoids, most notably in PPMS, we observed a decrease of proliferation marker Ki67 and a reduction of the SOX2+ stem cell pool associated with an increased expression of neuronal markers CTIP2 and TBR1 as well as a strong decrease of oligodendrocyte differentiation. This dysregulation of the stem cell pool is associated with a decreased expression of the cell cycle inhibitor p21. Our findings show that the genetic background of a patient can directly alter stem cell function, provides new insights on the innate cellular dysregulation in MS and identifies p21 pathway as a new potential target for therapeutic strategies in MS.
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