Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome
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. Down...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Research
2025
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| Online Access: | http://psasir.upm.edu.my/id/eprint/120219/ http://psasir.upm.edu.my/id/eprint/120219/1/120219.pdf |
| _version_ | 1848868140113461248 |
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| author | Tan, Huang Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa |
| author_facet | Tan, Huang Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa |
| author_sort | Tan, Huang |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T14:47:39Z |
| format | Article |
| id | upm-120219 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:47:39Z |
| publishDate | 2025 |
| publisher | Nature Research |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1202192025-09-25T07:09:21Z http://psasir.upm.edu.my/id/eprint/120219/ Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome Tan, Huang Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa 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. Nature Research 2025 Article PeerReviewed text en cc_by_nc_nd_4 http://psasir.upm.edu.my/id/eprint/120219/1/120219.pdf Tan, Huang and Fakurazi, Sharida and Cheah, Pike-See and Ling, King-Hwa (2025) Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome. Scientific Reports, 15 (1). art. no. 2818. pp. 1-17. ISSN 2045-2322 https://www.nature.com/articles/s41598-025-87314-y?error=cookies_not_supported&code=25271904-06cf-4c36-919f-f75a848d47c9 10.1038/s41598-025-87314-y |
| spellingShingle | Tan, Huang Fakurazi, Sharida Cheah, Pike-See Ling, King-Hwa Dysregulation of REST and its target genes impacts the fate of neural progenitor cells in down syndrome |
| 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 |
| url | http://psasir.upm.edu.my/id/eprint/120219/ http://psasir.upm.edu.my/id/eprint/120219/ http://psasir.upm.edu.my/id/eprint/120219/ http://psasir.upm.edu.my/id/eprint/120219/1/120219.pdf |