The interplay between miRNAs and chromatin regulators underpins premature differentiation within neurodevelopmental disorders (NDDs)
Wood, J. S.; Alsqati, M.; Harwood, A. J.
Show abstract
Neurodevelopmental disorders (NDDs), such as Schizophrenia, Autism and Intellectual disability (ID) possess a wide range of neurological and physiological phenotypes, often showing significant overlap. Epigenetic regulators, including miRNAs and chromatin modifiers, have long been proposed as a possible cause of the broad range of symptoms associated with NDDs. However, the inherent complexity within miRNA regulatory networks has made it challenging to identify the key miRNAs and their mRNA targets and how they lead to the molecular deficits seen in NDDs. Here we investigate a regulatory pathway that connects the epigenetic repressor EHMT1 to the miRNA network to control REST/NRSF protein expression and show that it controls the timing of neurodevelopment. By use of a novel strategy utilising multi-miR sponges we identify key miRNAs that regulate REST/NRSF in human induced pluripotent stem cells (iPSC) and demonstrate that they control unidirectional developmental progression from the pluripotent stage into early neurodevelopment and then neuronal differentiation. These results demonstrate a highly regulated interaction between epigenetic regulators and miRNAs that is crucial to control the timing neurodevelopment and impacts on the origins of NDDs.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Epigenome and transcriptome changes in KMT2D-related Kabuki syndrome Type 1 iPSCs, neuronal progenitors and cortical neurons 95%
- miRNA-mediated loss of m6A increases nascent translation in glioblastoma 95%
- Genomic features underlie the co-option of SVA transposons as cis-regulatory elements in human pluripotent stem cells 93%
Similar papers in this journal
- Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome 96%
- Familial ALS/FTD-associated RNA-Binding deficient TDP-43 mutants cause neuronal and synaptic transcript dysregulation in vitro 94%
- Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT 94%
Similar papers in this journal
- Integrative transcriptomics and electrophysiological profiling of hiPSC-derived neurons identifies novel druggable pathways in Koolen-de Vries Syndrome 94%
- Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage 93%
- Molecular consequences of PQBP1 deficiency, involved in the X-linked Renpenning syndrome 93%
Similar papers in this journal
- Deciphering the role of the lncRNA TRIBAL in hepatocyte models 94%
- Shared and distinct microRNA profiles between HT22, N2A and SH-SY5Y cell lines and primary mouse hippocampal neurons 94%
- Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis 92%
Similar papers in this journal
- Impaired p53-mediated DNA damage response contributes to microcephaly in Nijmegen Breakage Syndrome patient-derived cerebral organoids 94%
- Cockayne syndrome patient iPSC-derived brain organoids and neurospheres show early transcriptional dysregulation of biological processes associated with brain development and metabolism. 93%
- Functional characterization of Neurofilament Light b splicing and misbalance in zebrafish 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.