ArticleStem cell research & therapy2015
Loss of non-coding RNA expression from the DLK1-DIO3 imprinted locus correlates with reduced neural differentiation potential in human embryonic stem cell lines.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 336 citations in OpenAlex.
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- Dual Role of DLK1 in GnRH Neuron Ontogeny.Stem cell reviews and reports · 2025Article
- Why are imprints unstable in pluripotent stem cells?Biochemical Society transactions · 2025Article
- Effects of alcohol on the transcriptome, methylome and metabolome of in vitro gastrulating human embryonic cells.Disease models & mechanisms · 2025Article
- MEG8 as an antagonistic pleiotropic mechanism in breast cancer.Cell death discovery · 2024Article
- Donor Sex and Passage Conditions Influence MSC Osteogenic Response in Mineralized Collagen Scaffolds.Advanced healthcare materials · 2024Article
- Chronically high stress hormone levels dysregulate sperm long noncoding RNAs and their embryonic microinjection alters development and affective behaviours.Molecular psychiatry · 2024Article
- Variation of DNA methylation on theRegenerative therapy · 2022Article
- miR-31-5p from placental and peripheral blood exosomes is a potential biomarker to diagnose preeclampsia.Hereditas · 2022Article
- Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation.Nature communications · 2022Article
- Identification of the porcine IG-DMR and abnormal imprinting ofFrontiers in cell and developmental biology · 2022Article
- A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus.Developmental cell · 2021Article
- Long Non-Coding RNA MEG3 in Cellular Stemness.International journal of molecular sciences · 2021Review
- Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm.Scientific reports · 2021Article
- Maternally expressed gene 3 in metabolic programming.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- LncRNA Functions as a New Emerging Epigenetic Factor in Determining the Fate of Stem Cells.Frontiers in genetics · 2020Review
- Expression of miRNAs from the ImprintedCells · 2019Article
- RNA-seq of Isolated Chromaffin Cells Highlights the Role of Sex-Linked and Imprinted Genes in Adrenal Medulla Development.Scientific reports · 2019Article
- Lateral transfer of organophosphate degradation (Journal of genetics · 2019Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPluripotent stem cells are increasingly used to build therapeutic models, including the transplantation of neural progenitors derived from human embryonic stem cells (hESCs). Recently, long non-coding RNAs (lncRNAs), including delta-like homolog 1 gene and the type III iodothyronine deiodinase gene (DLK1-DIO3) imprinted locus-derived maternally expressed gene 3 (MEG3), were found to be expressed during neural development. The deregulation of these lncRNAs is associated with various neurological diseases. The imprinted locus DLK1-DIO3 encodes abundant non-coding RNAs (ncRNAs) that are regulated by differential methylation of the locus. We aim to study the correlation between the DLK1-DIO3-derived ncRNAs and the capacity of hESCs to differentiate into neural lineages.
methodsWe classified hESC sublines into MEG3-ON and MEG3-OFF based on the expression levels of MEG3 and its downstream microRNAs as detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A cDNA microarray was used to analyze the gene expression profiles of hESCs. To investigate the capacity of neural differentiation in MEG3-ON and MEG3-OFF hESCs, we performed neural lineage differentiation followed by neural lineage marker expression and neurite formation analyses via qRT-PCR and immunocytochemistry, respectively. MEG3-knockdown via small interfering RNA (siRNA) and small hairpin RNA (shRNA) was used to investigate the potential causative effect of MEG3 in regulating neural lineage-related gene expression.
resultsDLK1-DIO3-derived ncRNAs were repressed in MEG3-OFF hESCs compared with those in the MEG3-ON hESCs. The transcriptome profile indicated that many genes related to nervous system development and neural-type tumors were differentially expressed in MEG3-OFF hESCs. Three independent MEG3-knockdown assays using different siRNA and shRNA constructs consistently resulted in downregulation of some neural lineage genes. Lower expression levels of stage-specific neural lineage markers and reduced neurite formation were observed in neural lineage-like cells derived from MEG3-OFF-associated hESCs compared with those in the MEG3-ON groups at the same time points after differentiation.
conclusionsRepression of ncRNAs derived from the DLK1-DIO3 imprinted locus is associated with reduced neural lineage differentiation potential in hESCs.
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