Networks of Cultured iPSC-Derived Neurons Reveal the Human Synaptic Activity-Regulated Adaptive Gene Program
Open accessAbstract
Long-term adaptive responses in the brain, such as learning and memory, require synaptic activity-regulated gene expression, which has been thoroughly investigated in rodents. Using human iPSC-derived neuronal networks, we show that the human and the mouse synaptic activity-induced transcriptional programs share many genes and both require Ca 2+ -regulated synapse-to-nucleus signaling. Species-specific differences include the noncoding RNA genes BRE - AS1 and LINC00473 and the protein-coding gene ZNF331 , which are absent in the mouse genome, as well as several human genes whose orthologs are either not induced by activity or are induced with different kinetics in mice. These results indicate that lineage-specific gain of genes and DNA regulatory elements affects the synaptic activity-regulated gene program, providing a mechanism driving the evolution of human cognitive abilities.
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LINC00473 is regulated by synaptic activity and downregulates immediate early gene expression.
“LINC00473 is regulated by synaptic activity and downregulates immediate early gene expression (74)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [74]
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References 52 · Cited by 78
- Authors
- Pruunsild, P., Bengtson, C. P., & Bading, H.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Bading, Hilmar
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 18
- Issue
- 1
- Pages
- 122-135
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5236011
- OpenAlex
- W2571537593
- Cited by
- 78
- References
- 52
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 12 · 2023: 6 · 2022: 13 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 7 · 2017: 2
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- ERC Advanced Grant
- German-Israeli Project Cooperation
- Excellence Cluster CellNetworks at Heidelberg University
- SFB (1134)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- iPSC-derived neurons, neuronal networks, activity-dependent transcription, calcium signaling, non-coding RNA, LINC00473, ZNF331, human cognitive evolution, learning and memory
- MeSH terms
- Animals, Base Sequence, Bicuculline, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Neurons, Promoter Regions, Genetic, Species Specificity, Synapses, Signal Transduction, 4-Aminopyridine, Genes, Immediate-Early, Cell Lineage, Calcium Signaling, Mice, Electrophysiological Phenomena, Induced Pluripotent Stem Cells
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