The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Genetic Screen for Cell Fitness in High or Low Oxygen Highlights Mitochondrial and Lipid Metabolism
Open accessAbstract
Human cells are able to sense and adapt to variations in oxygen levels. Historically, much research in this field has focused on hypoxia-inducible factor (HIF) signaling and reactive oxygen species (ROS). Here, we perform genome-wide CRISPR growth screens at 21%, 5%, and 1% oxygen to systematically identify gene knockouts with relative fitness defects in high oxygen (213 genes) or low oxygen (109 genes), most without known connection to HIF or ROS. Knockouts of many mitochondrial pathways thought to be essential, including complex I and enzymes in Fe-S biosynthesis, grow relatively well at low oxygen and thus are buffered by hypoxia. In contrast, in certain cell types, knockout of lipid biosynthetic and peroxisomal genes causes fitness defects only in low oxygen. Our resource nominates genetic diseases whose severity may be modulated by oxygen and links hundreds of genes to oxygen homeostasis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Many autophagy-related genes were also common hits in the two screens (Fig. 2 d,e), such as WIPI2, ATG9A, ATG13, ATG14, and BECN1, suggesting an important role of autophagy in maintaining redox homeostasis in cells, as reported in previous studies31–33.”
From Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis (2021) · cites this paper as [33]
In the citing paper
“Many autophagy-related genes were also common hits in the two screens (Fig. 2 d,e), such as WIPI2, ATG9A, ATG13, ATG14, and BECN1, suggesting an important role of autophagy in maintaining redox homeostasis in cells, as reported in previous studies31–33.”
From Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis (2021) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Self-citationTrapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 12,145
KEGG as a reference resource for gene and protein annotation
Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1070 · Cited by 7,387
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders
Hamosh, A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki033 · Cited by 3,443
Defining a Cancer Dependency Map
Tsherniak, A., Vazquez, F., Montgomery, P. G., Weir, B. A., Kryukov, G., Cowley, G. S., Gill, S., Harrington, W. F., Pantel, S., Krill-Burger, J. M., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.010 · Cited by 3,276
Li, W., Xu, H., Xiao, T., Cong, L., Love, M. I., Zhang, F., Irizarry, R. A., Liu, J. S., Brown, M., & Liu, X. S. (2014) · Genome Biology · doi:10.1186/s13059-014-0554-4 · Cited by 2,684
Meyers, R. M., Bryan, J. G., McFarland, J. M., Weir, B. A., Sizemore, A. E., Xu, H., Dharia, N. V., Montgomery, P. G., Cowley, G. S., Pantel, S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3984 · Cited by 1,952
Mi, H., Muruganujan, A., & Thomas, P. D. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1118 · Cited by 1,739
Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude
Yi, X., Liang, Y., Huerta-Sanchez, E., Jin, X., Cuo, Z. X. P., Pool, J. E., Xu, X., Jiang, H., Vinckenbosch, N., Korneliussen, T. S., et al. (2010) · Science · doi:10.1126/science.1190371 · Cited by 1,611 · cited 1×
“These studies have identified polymorphisms in the canonical vHL-PHD-HIF O2 sensing pathways (Beall et al., 2010; Peng et al., 2011; Simonson et al., 2010; Xu et al., 2011; Yang et al., 2017; Yi et al., 2010), representing the most rapid known example of recent natural selection.”
Cited by
Sorted by citations
Oughtred, R., Rust, J., Chang, C., Breitkreutz, B., Stark, C., Willems, A., Boucher, L., Leung, G., Kolas, N., Zhang, F., et al. (2021) · Protein Science · doi:10.1002/pro.3978 · Cited by 1,858
Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers
Soula, M., Weber, R. A., Zilka, O., Alwaseem, H., La, K., Yen, F. S., Molina, H., García‐Bermúdez, J., Pratt, D. A., & Birsoy, K. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0613-y · Cited by 774
Bock, C., Datlinger, P., Chardon, F. M., Coelho, M. A., Dong, M. B., Lawson, K. A., Lu, T., Maroc, L., Norman, T. M., Song, B., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00093-4 · Cited by 641
Therapeutic targeting of the hypoxic tumour microenvironment
Singleton, D. C., Macann, A., & Wilson, W. R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00539-4 · Cited by 507
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Tian, R., Abarientos, A., Hong, J., Hashemi, S. H., Yan, R., Dräger, N., Leng, K., Nalls, M. A., Singleton, A. B., Xu, K., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00862-0 · Cited by 414
Metadata
- Authors
- Jain, I. H., Calvo, S. E., Markhard, A. L., Skinner, O. S., To, T.-L., Ast, T., & Mootha, V. K.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Mootha, Vamsi K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 181
- Issue
- 3
- Pages
- 716-727.e11
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7293541
- OpenAlex
- W3014660178
- Semantic Scholar
- f5cf6ffc17c0afcf964c1821338eea659750c183
- Cited by
- 224
- References
- 71
- Citations by year
- 2026: 30 · 2025: 42 · 2024: 33 · 2023: 37 · 2022: 30 · 2021: 37 · 2020: 14
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Institutes of Health (1F32GM133047-01)
- J. Willard and Alice S. Marriott Foundation
- U.S. Department of Energy
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- oxygen homeostasis, hypoxia, cell fitness, genome-wide CRISPR screen, mitochondrial metabolism, lipid metabolism, complex I, peroxisomes, lipogenesis, hypoxia-inducible factor, reactive oxygen species
- MeSH terms
- Hypoxia, Genetic Testing, Humans, Lipids, Mitochondria, Oxygen, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, K562 Cells, Lipid Metabolism, Genome-Wide Association Study, HEK293 Cells, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
