Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST
in neuronal development, neuroinflammation, myelination, and
therapeutic responses within cerebral organoids in the context of
Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced
H9 cells, and the mature organoids were subsequently treated with
either FTY720 or DMF. Gene expression related to inflammation and
myelination was subsequently analyzed via qRT-PCR. Immunofluorescence
staining was used to assess the expression of proteins related to
inflammation, myelination, and neuronal differentiation. Alpha-synuclein
protein levels were also checked via ELISA. Finally, transcriptome
analysis was conducted on the organoid samples. Results: XIST-silenced
organoids presented a 2-fold increase in the expression of neuronal
stem cells, excitatory neurons, microglia, and mature oligodendrocyte
markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST
silencing tripled IBA1 protein expression, it did not affect organoid
MBP expression. FTY720, but not DMF, distinguished MBP and IBA1
expression in XIST-silenced organoids. Furthermore, XIST
silencing reduced the concentration of alpha-synuclein from 300 to 100
pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene
enrichment analyses revealed that the differentially expressed genes are
involved in neural development and immune processes, suggesting the
role of XIST in neuroinflammation. The
silencing of XIST modified the expression of genes associated with
inflammation, myelination, and neuronal growth in cerebral organoids,
indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST
may contribute to the MS pathogenesis as well as neuroinflammatory
diseases such as and Alzheimer’s and Parkinson’s diseases and may be a
promising therapeutic target.
Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST
in neuronal development, neuroinflammation, myelination, and
therapeutic responses within cerebral organoids in the context of
Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced
H9 cells, and the mature organoids were subsequently treated with
either FTY720 or DMF. Gene expression related to inflammation and
myelination was subsequently analyzed via qRT-PCR. Immunofluorescence
staining was used to assess the expression of proteins related to
inflammation, myelination, and neuronal differentiation. Alpha-synuclein
protein levels were also checked via ELISA. Finally, transcriptome
analysis was conducted on the organoid samples. Results: XIST-silenced
organoids presented a 2-fold increase in the expression of neuronal
stem cells, excitatory neurons, microglia, and mature oligodendrocyte
markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST
silencing tripled IBA1 protein expression, it did not affect organoid
MBP expression. FTY720, but not DMF, distinguished MBP and IBA1
expression in XIST-silenced organoids. Furthermore, XIST
silencing reduced the concentration of alpha-synuclein from 300 to 100
pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene
enrichment analyses revealed that the differentially expressed genes are
involved in neural development and immune processes, suggesting the
role of XIST in neuroinflammation. The
silencing of XIST modified the expression of genes associated with
inflammation, myelination, and neuronal growth in cerebral organoids,
indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST
may contribute to the MS pathogenesis as well as neuroinflammatory
diseases such as and Alzheimer’s and Parkinson’s diseases and may be a
promising therapeutic target.