論文 - 詳細
| RRC ID | 82823 |
|---|---|
| 著者 | Huang T, Fakurazi S, Cheah PS, Ling KH. |
| タイトル | Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome. |
| ジャーナル | Sci Rep |
| Abstract |
Increasing shreds of evidence suggest that neurogenic-to-gliogenic shift may be critical to the abnormal neurodevelopment observed in individuals with Down syndrome (DS). REST, the Repressor Element-1 Silencing Transcription factor, regulates the differentiation and development of neural cells. Downregulation of REST may lead to defects in post-differentiation neuronal morphology in the brain of the DS fetal. This study aims to elucidate the role of REST in DS-derived NPCs using bioinformatics analyses and laboratory validations. We identified and validated vital REST-targeted DEGs: CD44, TGFB1, FN1, ITGB1, and COL1A1. Interestingly, these genes are involved in neurogenesis and gliogenesis in DS-derived NPCs. Furthermore, we identified nuclear REST loss and the neuroblast marker, DCX, was downregulated in DS human trisomic induced pluripotent stem cells (hiPSCs)-derived NPCs, whereas the glioblast marker, NFIA, was upregulated. Our findings indicate that the loss of REST is critical in the neurogenic-to-gliogenic shift observed in DS-derived NPCs. REST and its target genes may collectively regulate the NPC phenotype. |
| 巻・号 | 15(1) |
| ページ | 2818 |
| 公開日 | 2025-1-22 |
| DOI | 10.1038/s41598-025-87314-y |
| PII | 10.1038/s41598-025-87314-y |
| PMID | 39843579 |
| PMC | PMC11754635 |
| MeSH | Cell Differentiation / genetics Computational Biology / methods Doublecortin Protein* Down Syndrome* / genetics Down Syndrome* / metabolism Down Syndrome* / pathology Gene Expression Regulation Humans Hyaluronan Receptors Induced Pluripotent Stem Cells* / metabolism Integrin beta1 / genetics Integrin beta1 / metabolism NFI Transcription Factors / genetics NFI Transcription Factors / metabolism Neural Stem Cells* / metabolism Neurogenesis* / genetics Repressor Proteins* / genetics Repressor Proteins* / metabolism Transforming Growth Factor beta1 / genetics Transforming Growth Factor beta1 / metabolism |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HPS4272(HPS4272) HPS4270(HPS4270) |