Genes essential for embryonic stem cells are associated with neurodevelopmental disorders
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Abstract
Mouse embryonic stem cells (mESCs) are key components in generating mouse models for human diseases and performing basic research on pluripotency, yet the number of genes essential for mESCs is still unknown. We performed a genome-wide screen for essential genes in mESCs and compared it to screens in human cells. We found that essential genes are enriched for basic cellular functions, are highly expressed in mESCs, and tend to lack paralog genes. We discovered that genes that are essential specifically in mESCs play a role in pathways associated with their pluripotent state. We show that 29.5% of human genes intolerant to loss-of-function mutations are essential in mouse or human ESCs, and that the human phenotypes most significantly associated with genes essential for ESCs are neurodevelopmental. Our results provide insights into essential genes in the mouse, the pathways which govern pluripotency, and suggest that many genes associated with neurodevelopmental disorders are essential at very early embryonic stages.
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Cites
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MethodIdentification and characterization of essential genes in the human genome
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- Authors
- Shohat, S., & Shifman, S.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Shifman, Sagiv
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2019-10-24
- Volume
- 29
- Issue
- 11
- Pages
- 1910-1918
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC6836742
- OpenAlex
- W2981850605
- Cited by
- 21
- References
- 8
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 2
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Israel Science Foundation (575/17)
- Israel Science Foundation Broad Institute Joint Program (2612/18)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- mouse embryonic stem cells, essential genes, neurodevelopmental disorders, pluripotency, loss-of-function intolerance, human disease models, human-mouse comparison
- MeSH terms
- Human Embryonic Stem Cells, Mouse Embryonic Stem Cells, Loss of Function Mutation, Animals, Heterozygote, Homozygote, Humans, Mice, Clustered Regularly Interspaced Short Palindromic Repeats, Neurodevelopmental Disorders
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