{"doi":"10.1371/journal.pgen.1009286","title":"GATA factor-regulated solute carrier ensemble reveals a nucleoside transporter-dependent differentiation mechanism","abstract":"Developmental-regulatory networks often include large gene families encoding mechanistically-related proteins like G-protein-coupled receptors, zinc finger transcription factors and solute carrier (SLC) transporters. In principle, a common mechanism may confer expression of multiple members integral to a developmental process, or diverse mechanisms may be deployed. Using genetic complementation and enhancer-mutant systems, we analyzed the 456 member SLC family that establishes the small molecule constitution of cells. This analysis identified SLC gene cohorts regulated by GATA1 and/or GATA2 during erythroid differentiation. As >50 SLC genes shared GATA factor regulation, a common mechanism established multiple members of this family. These genes included Slc29a1 encoding an equilibrative nucleoside transporter (Slc29a1/ENT1) that utilizes adenosine as a preferred substrate. Slc29a1 promoted erythroblast survival and differentiation ex vivo. Targeted ablation of murine Slc29a1 in erythroblasts attenuated erythropoiesis and erythrocyte regeneration in response to acute anemia. Our results reveal a GATA factor-regulated SLC ensemble, with a nucleoside transporter component that promotes erythropoiesis and prevents anemia, and establish a mechanistic link between GATA factor and adenosine mechanisms. We propose that integration of the GATA factor-adenosine circuit with other components of the GATA factor-regulated SLC ensemble establishes the small molecule repertoire required for progenitor cells to efficiently generate erythrocytes.","journal":"PLoS Genetics","year":2020,"id":77096,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"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":228525,"name":"Xiaoli Cai","orcid":"0009-0003-2137-2751","position":1,"is_corresponding":false},{"id":333662,"name":"Ruiqi Liao","orcid":"0000-0002-9553-3349","position":2,"is_corresponding":false},{"id":401933,"name":"Bin Mao","orcid":"0000-0002-3792-3787","position":3,"is_corresponding":false},{"id":401934,"name":"Daniel Conn","orcid":"0000-0003-1788-2858","position":4,"is_corresponding":false},{"id":401935,"name":"Charu Mehta","orcid":"0000-0002-8644-3333","position":5,"is_corresponding":false},{"id":43259,"name":"Sündüz Keleş","orcid":"0000-0001-9048-0922","position":6,"is_corresponding":false},{"id":297839,"name":"Yang Xia","orcid":"0000-0002-8059-6179","position":7,"is_corresponding":false},{"id":333666,"name":"Emery H. Bresnick","orcid":"0000-0002-1151-5654","position":8,"is_corresponding":false},{"id":401932,"name":"Nicole M. Zwifelhofer","orcid":"0000-0001-9577-3994","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T21:48:50.085103Z","pmid":"33370779","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":[]}