{"doi":"10.1084/jem.20191526","title":"Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories","abstract":"Stem and progenitor cell fate transitions constitute key decision points in organismal development that enable access to a developmental path or actively preclude others. Using the hematopoietic system, we analyzed the relative importance of cell fate-promoting mechanisms versus negating fate-suppressing mechanisms to engineer progenitor cells with multilineage differentiation potential. Deletion of the murine Gata2-77 enhancer, with a human equivalent that causes leukemia, downregulates the transcription factor GATA2 and blocks progenitor differentiation into erythrocytes, megakaryocytes, basophils, and granulocytes, but not macrophages. Using multiomics and single-cell analyses, we demonstrated that the enhancer orchestrates a balance between pro- and anti-fate circuitry in single cells. By increasing GATA2 expression, the enhancer instigates a fate-promoting mechanism while abrogating an innate immunity-linked, fate-suppressing mechanism. During embryogenesis, the suppressing mechanism dominated in enhancer mutant progenitors, thus yielding progenitors with a predominant monocytic differentiation potential. Coordinating fate-promoting and -suppressing circuits therefore averts deconstruction of a multifate system into a monopotent system and maintains critical progenitor heterogeneity and functionality.","journal":"The Journal of Experimental Medicine","year":2020,"id":91837,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":401934,"name":"Daniel Conn","orcid":"0000-0003-1788-2858","position":1,"is_corresponding":false},{"id":109552,"name":"Evgenia Shishkova","orcid":"0000-0001-6097-6097","position":2,"is_corresponding":false},{"id":438088,"name":"Koichi R. Katsumura","orcid":"0000-0002-1523-0533","position":3,"is_corresponding":false},{"id":459568,"name":"Peng Liu","orcid":"0000-0001-5655-2259","position":4,"is_corresponding":false},{"id":459569,"name":"Siqi Shen","orcid":"0000-0003-1661-1247","position":5,"is_corresponding":false},{"id":336005,"name":"Erik A. Ranheim","orcid":"0000-0002-5786-9327","position":6,"is_corresponding":false},{"id":298760,"name":"Sean G. Kraus","orcid":"0009-0001-6010-2936","position":7,"is_corresponding":false},{"id":459570,"name":"Weixin Wang","orcid":"0000-0001-7693-3374","position":8,"is_corresponding":false},{"id":218270,"name":"Katherine R. Calvo","orcid":"0000-0002-0771-4191","position":9,"is_corresponding":false},{"id":362027,"name":"Amy P. Hsu","orcid":"0000-0001-6841-2122","position":10,"is_corresponding":false},{"id":104227,"name":"Steven M. Holland","orcid":"0000-0003-3207-5464","position":11,"is_corresponding":false},{"id":71208,"name":"Joshua J. Coon","orcid":"0000-0002-0004-8253","position":12,"is_corresponding":false},{"id":43259,"name":"Sündüz Keleş","orcid":"0000-0001-9048-0922","position":13,"is_corresponding":false},{"id":333666,"name":"Emery H. Bresnick","orcid":"0000-0002-1151-5654","position":14,"is_corresponding":false},{"id":459567,"name":"Kirby D. Johnson","orcid":"0000-0003-0236-7482","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-18T22:29:21.932251Z","pmid":"32736380","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":[]}