{"doi":"10.1182/blood.2019004688","title":"Role of c-Myc haploinsufficiency in the maintenance of HSCs in mice","abstract":"This study was conducted to determine the dosage effect of c-Myc on hematopoiesis and its distinct role in mediating the Wnt/β-catenin pathway in hematopoietic stem cell (HSC) and bone marrow niche cells. c-Myc haploinsufficiency led to ineffective hematopoiesis by inhibiting HSC self-renewal and quiescence and by promoting apoptosis. We have identified Nr4a1, Nr4a2, and Jmjd3, which are critical for the maintenance of HSC functions, as previously unrecognized downstream targets of c-Myc in HSCs. c-Myc directly binds to the promoter regions of Nr4a1, Nr4a2, and Jmjd3 and regulates their expression. Our results revealed that Nr4a1 and Nr4a2 mediates the function of c-Myc in regulating HSC quiescence, whereas all 3 genes contribute to the function of c-Myc in the maintenance of HSC survival. Adenomatous polyposis coli (Apc) is a negative regulator of the Wnt/β-catenin pathway. We have provided the first evidence that Apc haploinsufficiency induces a blockage of erythroid lineage differentiation through promoting secretion of IL6 in bone marrow endothelial cells. We found that c-Myc haploinsufficiency failed to rescue defective function of Apc-deficient HSCs in vivo but it was sufficient to prevent the development of severe anemia in Apc-heterozygous mice and to significantly prolong the survival of those mice. Furthermore, we showed that c-Myc-mediated Apc loss induced IL6 secretion in endothelial cells, and c-Myc haploinsufficiency reversed the negative effect of Apc-deficient endothelial cells on erythroid cell differentiation. Our studies indicate that c-Myc has a context-dependent role in mediating the function of Apc in hematopoiesis.","journal":"Blood","year":2020,"id":63075,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"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":333752,"name":"Rui Ma","orcid":"0000-0002-1441-6862","position":1,"is_corresponding":false},{"id":333753,"name":"Chunjie Yu","orcid":"0000-0003-2161-3394","position":2,"is_corresponding":false},{"id":333754,"name":"Qiong Wu","orcid":"0000-0002-9514-9937","position":3,"is_corresponding":false},{"id":335478,"name":"Steven Zhang","orcid":null,"position":4,"is_corresponding":false},{"id":335479,"name":"Kimberly Paulsen","orcid":null,"position":5,"is_corresponding":false},{"id":294082,"name":"Jiwang Zhang","orcid":"0000-0003-4309-2892","position":6,"is_corresponding":false},{"id":333755,"name":"Hongyu Ni","orcid":"0000-0002-7597-2037","position":7,"is_corresponding":false},{"id":333756,"name":"Yong Huang","orcid":"0009-0001-1989-8223","position":8,"is_corresponding":false},{"id":333757,"name":"Yi Zheng","orcid":"0000-0001-7089-6074","position":9,"is_corresponding":false},{"id":230600,"name":"Zhijian Qian","orcid":"0000-0001-5565-7534","position":10,"is_corresponding":false},{"id":1665,"name":"Yue Sheng","orcid":"0000-0002-9424-123X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T21:11:00.632961Z","pmid":"33538795","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":[]}