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.

AUTHORS: Tan Huang, Sharida Fakurazi, Pike-See Cheah & King-Hwa Ling

SOURCE TITLE: Scientific Reports

VOLUME:15

YEAR: 2025

ISSN OR ISBN: 2045-2322

RANK BY JOURNAL IMPACT FACTOR (JIF): Q1

DOI: https://doi.org/10.1038/s41598-025-87314-y 

Date of Input: 25/08/2025 | Updated: 12/11/2025 | nadia_rahman