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Cited by 160CRISPR and Genetic EngineeringGenomics and Chromatin DynamicsMicrotubule and mitosis dynamics

The phenotypic landscape of essential human genes

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Funk, Luke, Su, Kuan-Chung, Ly, Jimmy, Feldman, David, Singh, Avtar, Moodie, Brittania, Blainey, Paul C., Cheeseman, Iain M.·2022·Cell
DOI 10.1016/j.cell.2022.10.017PMC PMC10482496

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Abstract

Understanding the basis for cellular growth, proliferation, and function requires determining the roles of essential genes in diverse cellular processes, including visualizing their contributions to cellular organization and morphology. Here, we combined pooled CRISPR-Cas9-based functional screening of 5,072 fitness-conferring genes in human HeLa cells with microscopy-based imaging of DNA, the DNA damage response, actin, and microtubules. Analysis of >31 million individual cells identified measurable phenotypes for >90% of gene knockouts, implicating gene targets in specific cellular processes. Clustering of phenotypic similarities based on hundreds of quantitative parameters further revealed co-functional genes across diverse cellular activities, providing predictions for gene functions and associations. By conducting pooled live-cell screening of ∼450,000 cell division events for 239 genes, we additionally identified diverse genes with functional contributions to chromosome segregation. Our work establishes a resource detailing the consequences of disrupting core cellular processes that represents the functional landscape of essential human genes.

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Cited by

Sorted by citations

Authors
Funk, L., Su, K.-C., Ly, J., Feldman, D., Singh, A., Moodie, B., Blainey, P. C., & Cheeseman, I. M.
Affiliations
  • Broad Institute (US)
  • Whitehead Institute for Biomedical Research (US)
Corresponding author
  • Blainey, Paul C.
  • Cheeseman, Iain M.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2022-11
Volume
185
Issue
24
Pages
4634-4653.e22
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2022.10.017
PMC
PMC10482496
OpenAlex
W4308435054
Cited by
160
References
17
Citations by year
2026: 30 · 2025: 51 · 2024: 39 · 2023: 27 · 2022: 12 · 2019: 1
FWCI
10.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Gordon and Betty Moore Foundation
  • Broad Institute
  • National Institutes of Health (5rm1hg006193-10)
  • National Defense Science and Engineering Graduate
  • National Human Genome Research Institute (RM1‐HG006193, P50HG006193, R01HG009283)
  • National Institute of General Medical Sciences (R35GM126930)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
HeLa cells, DNA damage response, actin, microtubules, chromosome segregation, cell division, live-cell imaging, gene function prediction
MeSH terms
HeLa Cells, Humans, Phenotype, Genes, Essential, Gene Knockout Techniques, CRISPR-Cas Systems

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