ArticlePloS one2019
Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Meta-Analysis IdentifiesInternational journal of molecular sciences · 2022Pooled it
- The role of astrocytes in autism spectrum disorder and associated syndromes: Evidence, animal models, mechanisms, and therapeutic potential.Zoological research · 2026Review
- Tet3-mediated DNA demethylation is essential for maintaining the dedifferentiation capacity of mammalian Müller glia.Frontiers in molecular neuroscience · 2025Article
- MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- The omics era: a nexus of untapped potential for Mendelian chromatinopathies.Human genetics · 2024Review
- Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency.iScience · 2024Article
- Neural lineage differentiation of human pluripotent stem cells: Advances in disease modeling.World journal of stem cells · 2023Review
- Advances in the pathogenesis of Rett syndrome using cell models.Animal models and experimental medicine · 2022Review
- Modeling RTT Syndrome by iPSC-Derived Neurons from Male and Female Patients with Heterogeneously Severe Hot-Spot MECP2 Variants.International journal of molecular sciences · 2022Article
- LIN28A: A multifunctional versatile molecule with future therapeutic potential.World journal of biological chemistry · 2022Review
- Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density.Acta neuropathologica communications · 2021Article
- Article
- Review
- Proteomic and transcriptional changes associated with MeCP2 dysfunction reveal nodes for therapeutic intervention in Rett syndrome.Neurochemistry international · 2021Review
- Patient-Derived Induced Pluripotent Stem Cells (iPSCs) and Cerebral Organoids for Drug Screening and Development in Autism Spectrum Disorder: Opportunities and Challenges.Pharmaceutics · 2021Review
- Modeling Neurodevelopmental and Neuropsychiatric Diseases with Astrocytes Derived from Human-Induced Pluripotent Stem Cells.International journal of molecular sciences · 2021Review
- Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.Neuroscience and biobehavioral reviews · 2021Review
- Role and Regulation of Lin28 in Progenitor Cells During Central Nervous System Development.Advances in experimental medicine and biology · 2021Article
- Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models.Frontiers in neuroscience · 2021Review
- Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.