ArticleNature metabolism2020
Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 119 citations in OpenAlex.
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- Accurate profiling of single-cell alternative transcript start sites by correcting RNA degradation.Nature communications · 2026Article
- Expanding TheCellMap.org to visualize a genome-scale genetic interaction network for a human cell line.bioRxiv : the preprint server for biology · 2026Article
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
- Analysis of Combinatorial Knockout CRISPR Screens with GRAPE: Genetic interaction Regression Analysis of Pairwise Effects.bioRxiv : the preprint server for biology · 2026Article
- Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Tegavivint triggers TECR-dependent nonapoptotic cancer cell death.Nature chemical biology · 2025Article
- Lipid Metabolism-Signaling Crosstalk in Metabolic Disease and Aging: Mechanisms and Therapeutic Targets.Nutrients · 2025Review
- Lipid metabolism and lipid signaling in extracellular vesicles ontogeny: from biogenesis to functional execution.Journal of nanobiotechnology · 2025Review
- SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.Current opinion in lipidology · 2025Review
- Unique metabolic regulation of micromeres contributes to gastrulation in the sea urchin embryo.Nature communications · 2025Article
- Very long-chain fatty acids accumulate in breast cancer tissue and serum.Cancer cell international · 2025Article
- Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.Cancer communications (London, England) · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- BaCoN (Balanced Correlation Network) improves prediction of gene buffering.Molecular systems biology · 2025Article
- Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Impact of FASN-enriched EVs on endothelial cell function in obstructive sleep apnea hypopnea syndrome.Journal of pharmaceutical analysis · 2025Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 3 institutions in 2 countries.
Funding
Abstract
The de novo synthesis of fatty acids has emerged as a therapeutic target for various diseases, including cancer. Because cancer cells are intrinsically buffered to combat metabolic stress, it is important to understand how cells may adapt to the loss of de novo fatty acid biosynthesis. Here, we use pooled genome-wide CRISPR screens to systematically map genetic interactions (GIs) in human HAP1 cells carrying a loss-of-function mutation in fatty acid synthase (FASN), whose product catalyses the formation of long-chain fatty acids. FASN-mutant cells show a strong dependence on lipid uptake that is reflected in negative GIs with genes involved in the LDL receptor pathway, vesicle trafficking and protein glycosylation. Further support for these functional relationships is derived from additional GI screens in query cell lines deficient in other genes involved in lipid metabolism, including LDLR, SREBF1, SREBF2 and ACACA. Our GI profiles also identify a potential role for the previously uncharacterized gene C12orf49 (which we call LUR1) in regulation of exogenous lipid uptake through modulation of SREBF2 signalling in response to lipid starvation. Overall, our data highlight the genetic determinants underlying the cellular adaptation associated with loss of de novo fatty acid synthesis and demonstrate the power of systematic GI mapping for uncovering metabolic buffering mechanisms in human cells.
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