ArticleMolecular brain2021
Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons.
Article in Molecular brain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Elevation of the mechanically-sensitive e protein emerin links nuclear mechanotransduction to tau-induced cytoskeletal remodeling in neurons.Nucleus (Austin, Tex.) · 2026Article
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- Disease-associated mutations directionally modulate epigenetic age in iPSC-derived tissues.bioRxiv : the preprint server for biology · 2026Article
- Article
- Modeling medulloblastoma pathogenesis and treatment in human cerebellar organoids.Genes & development · 2026Article
- Psychosis as a multisystem disorder of aberrant aging.npj aging · 2026Review
- GluN2A-mediated currents and calcium signal in human iPSC-derived neurons.Scientific reports · 2026Article
- Developmental modulation of schizophrenia risk gene methylation in offspring exhibiting cognitive deficits following maternal immune activation.Molecular psychiatry · 2026Article
- Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex.Cell genomics · 2025Article
- A human iPSC-derived midbrain neural stem cell model of prenatal opioid exposure and withdrawal: A proof of concept study.PloS one · 2025Article
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Developmentally dynamic changes in DNA methylation in the human pancreas.BMC genomics · 2024Article
- Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration.Nature aging · 2024Review
- Epigenetic gestational age and the relationship with developmental milestones in early childhood.Human molecular genetics · 2023Article
- A human stem cell-derived neuronal model of morphine exposure reflects brain dysregulation in opioid use disorder: Transcriptomic and epigenetic characterization of postmortem-derived iPSC neurons.Frontiers in psychiatry · 2023Article
- Fountain of youth-Targeting autophagy in aging.Frontiers in aging neuroscience · 2023Review
- Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders.Neuroscience applied · 2023Review
- Conserved gene signatures shared amongFrontiers in molecular biosciences · 2023Article
- Attenuated transcriptional response to pro-inflammatory cytokines in schizophrenia hiPSC-derived neural progenitor cells.Brain, behavior, and immunity · 2022Article
- Developing Bottom-Up Induced Pluripotent Stem Cell Derived Solid Tumor Models Using Precision Genome Editing Technologies.The CRISPR journal · 2022Review
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Authors and funding
25 authors at 3 institutions in 2 countries.
Funding
Abstract
Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the earliest stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age. It has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, we developed the fetal brain clock (FBC), a bespoke epigenetic clock trained in human prenatal brain samples in order to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons. The FBC was tested in two independent validation cohorts across a total of 194 samples, confirming that the FBC outperforms other established epigenetic clocks in fetal brain cohorts. We applied the FBC to DNA methylation data from iPSCs and embryonic stem cells and their derived neuronal precursor cells and neurons, finding that these cell types are epigenetically characterized as having an early fetal age. Furthermore, while differentiation from iPSCs to neurons significantly increases epigenetic age, iPSC-neurons are still predicted as being fetal. Together our findings reiterate the need to better understand the limitations of existing epigenetic clocks for answering biological research questions and highlight a limitation of iPSC-neurons as a cellular model of age-related diseases.
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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.