{"doi":"10.1016/j.celrep.2021.110036","title":"Differentiation of fetal hematopoietic stem cells requires ARID4B to restrict autocrine KITLG/KIT-Src signaling","abstract":"Balance between the hematopoietic stem cell (HSC) duality to either possess self-renewal capacity or differentiate into multipotency progenitors (MPPs) is crucial for maintaining homeostasis of the hematopoietic stem/progenitor cell (HSPC) compartment. To retain the HSC self-renewal activity, KIT, a receptor tyrosine kinase, in HSCs is activated by its cognate ligand KITLG originating from niche cells. Here, we show that AT-rich interaction domain 4B (ARID4B) interferes with KITLG/KIT signaling, consequently allowing HSC differentiation. Conditional Arid4b knockout in mouse hematopoietic cells blocks fetal HSC differentiation, preventing hematopoiesis. Mechanistically, ARID4B-deficient HSCs self-express KITLG and overexpress KIT. As to downstream pathways of KITLG/KIT signaling, inhibition of Src family kinases rescues the HSC differentiation defect elicited by ARID4B loss. In summary, the intrinsic ARID4B-KITLG/KIT-Src axis is an HSPC regulatory program that enables the differentiation state, while KIT stimulation by KITLG from niche cells preserves the HSPC undifferentiated pool.","journal":"Cell Reports","year":2021,"id":160246,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":341850,"name":"Bogang Wu","orcid":"0000-0003-1654-198X","position":1,"is_corresponding":false},{"id":672641,"name":"Jaclyn Andricovich","orcid":"0000-0003-2945-5095","position":2,"is_corresponding":false},{"id":628501,"name":"Sung-Ting Chuang","orcid":"0000-0002-6433-2384","position":3,"is_corresponding":false},{"id":672642,"name":"Rong Li","orcid":"0000-0002-1805-810X","position":4,"is_corresponding":false},{"id":672643,"name":"Alexandros Tzatsos","orcid":"0000-0002-8476-4328","position":5,"is_corresponding":false},{"id":496150,"name":"Ray‐Chang Wu","orcid":"0000-0002-7142-0710","position":6,"is_corresponding":false},{"id":672644,"name":"Mei-Yi Wu","orcid":"0000-0002-0183-976X","position":7,"is_corresponding":false},{"id":673280,"name":"In-Chi Young","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:43.908634Z","pmid":"34818550","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":[]}