ArticleCell reports2024
Massively parallel disruption of enhancers active in human neural stem cells.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Multiscale Convergence of Signaling, Epigenetic, and Environmental Networks in Mammalian Palatogenesis and Cleft Palate Pathogenesis.International journal of stem cells · 2026Review
- Genome-Wide Annotation of Promoter-Enhancer Interactions via Chromatin Loops in the Hybrid Rat Diversity Panel.bioRxiv : the preprint server for biology · 2026Article
- Glioblastoma cells utilize evolutionarily adapted cell metabolism to promote their malignant proliferation.Acta neuropathologica communications · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- So Fragile, So Human: Noncoding DNA Regions Orchestrating Gene Expression Involved in Neurodevelopmental Disorders and in Human Brain Evolution.International journal of molecular sciences · 2026Review
- Cell-type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development.Cell genomics · 2025Article
- Epigenome and transcriptome changes in KMT2D-related Kabuki syndrome Type 1 iPSCs, neuronal progenitors and cortical neurons.PLoS genetics · 2025Article
- Article
- CRISPR-based functional genomics tools in vertebrate models.Experimental & molecular medicine · 2025Review
- Article
- Reconstructing human-specific regulatory functions in model systems.Current opinion in genetics & development · 2024Review
- How our brains are built: emerging approaches to understand human-specific features.Current opinion in genetics & development · 2024Review
- Evolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals.Molecular biology and evolution · 2024Article
- Massively parallel approaches for characterizing noncoding functional variation in human evolution.Current opinion in genetics & development · 2024Review
- Resolving the three-dimensional interactome of Human Accelerated Regions during human and chimpanzee neurodevelopment.bioRxiv : the preprint server for biology · 2024Article
- Evolutionary innovation in conserved regulatory elements across the mammalian tree of life.bioRxiv : the preprint server for biology · 2024Article
- Massively Parallel Reporter Assays: Defining Functional Psychiatric Genetic Variants Across Biological Contexts.Biological psychiatry · 2021Review
- Regulatory landscape in brain development and disease.Current opinion in genetics & development · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Changes in gene regulation have been linked to the expansion of the human cerebral cortex and to neurodevelopmental disorders, potentially by altering neural progenitor proliferation. However, the effects of genetic variation within regulatory elements on neural progenitors remain obscure. We use sgRNA-Cas9 screens in human neural stem cells (hNSCs) to disrupt 10,674 genes and 26,385 conserved regions in 2,227 enhancers active in the developing human cortex and determine effects on proliferation. Genes with proliferation phenotypes are associated with neurodevelopmental disorders and show biased expression in specific fetal human brain neural progenitor populations. Although enhancer disruptions overall have weaker effects than gene disruptions, we identify enhancer disruptions that severely alter hNSC self-renewal. Disruptions in human accelerated regions, implicated in human brain evolution, also alter proliferation. Integrating proliferation phenotypes with chromatin interactions reveals regulatory relationships between enhancers and their target genes contributing to neurogenesis and potentially to human cortical evolution.
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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.