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Updated: Aug 29, 2025

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
Non-coding RNAs associated with Prader-Willi syndrome regulate transcription of neurodevelopmental genes in human
Monika Sledziowska1, Kinga Winczura2, Matt Jones3
1School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Abstract:
Mutations and aberrant gene expression during cellular differentiation lead to neurodevelopmental disorders, such as Prader-Willi syndrome (PWS), which results from the deletion of an imprinted locus on paternally inherited chromosome 15. We analyzed chromatin-associated RNA in human induced pluripotent cells (iPSCs) upon depletion of hybrid small nucleolar long non-coding RNAs (sno-lncRNAs) and 5' snoRNA capped and polyadenylated long non-coding RNAs (SPA-lncRNAs) transcribed from the locus deleted in PWS. We found that rapid ablation of these lncRNAs affects transcription of specific gene classes. Downregulated genes contribute to neurodevelopment and neuronal maintenance, while upregulated genes are predominantly involved in the negative regulation of cellular metabolism and apoptotic processes. Our data reveal the importance of SPA-lncRNAs and sno-lncRNAs in controlling gene expression in iPSCs and provide a platform for synthetic experimental approaches in PWS studies. We conclude that ncRNAs transcribed from the PWS locus are critical regulators of a transcriptional signature, which is important for neuronal differentiation and development.
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