Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome
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 ce...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87314-y |
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| author | Tan Huang Sharida Fakurazi Pike-See Cheah King-Hwa Ling |
| author_facet | Tan Huang Sharida Fakurazi Pike-See Cheah King-Hwa Ling |
| author_sort | Tan Huang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-34fe3056d7034b9c97ee2b3153885623 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-34fe3056d7034b9c97ee2b31538856232025-01-26T12:32:35ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-025-87314-yDysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndromeTan Huang0Sharida Fakurazi1Pike-See Cheah2King-Hwa Ling3Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaAbstract 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.https://doi.org/10.1038/s41598-025-87314-yRESTNPCDown syndromeNeurogenesisGliogenesis |
| spellingShingle | Tan Huang Sharida Fakurazi Pike-See Cheah King-Hwa Ling Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome Scientific Reports REST NPC Down syndrome Neurogenesis Gliogenesis |
| title | Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome |
| title_full | Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome |
| title_fullStr | Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome |
| title_full_unstemmed | Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome |
| title_short | Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome |
| title_sort | dysregulation of rest and its target genes impacts the fate of neural progenitor cells in down syndrome |
| topic | REST NPC Down syndrome Neurogenesis Gliogenesis |
| url | https://doi.org/10.1038/s41598-025-87314-y |
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