{"doi":"10.1101/2023.03.19.533346","title":"Comparative landscape of genetic dependencies in human and chimpanzee stem cells","abstract":"Abstract Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether changes in human cells alter requirements for essential genes. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells, providing support for the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells can reshape the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392262,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9174,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":984940,"name":"Tyler Fair","orcid":null,"position":1,"is_corresponding":false},{"id":374699,"name":"Nathan K. Schaefer","orcid":"0000-0001-5881-7329","position":2,"is_corresponding":false},{"id":227687,"name":"Reuben A. Saunders","orcid":"0000-0003-3487-1579","position":3,"is_corresponding":false},{"id":96211,"name":"Bryan J. Pavlovic","orcid":"0000-0002-7751-5315","position":4,"is_corresponding":false},{"id":17890,"name":"Jonathan S. Weissman","orcid":"0000-0003-2445-670X","position":5,"is_corresponding":false},{"id":254660,"name":"Alex A. Pollen","orcid":"0000-0003-3263-8634","position":6,"is_corresponding":false},{"id":1042008,"name":"Richard She","orcid":"0000-0003-3056-3800","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T01:18:52.232318Z","pmid":"36993685","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}