{"doi":"10.1101/2021.05.04.442585","title":"Haploinsufficiency of the essential gene RpS12 causes defects in erythropoiesis and hematopoietic stem cell maintenance","abstract":"Abstract Ribosomal protein (Rp) gene haploinsufficiency can result in Diamond-Blackfan Anemia (DBA), characterized by defective erythropoiesis and skeletal defects. Some mouse Rp mutations recapitulate DBA phenotypes, although others lack erythropoietic or skeletal defects. We generated a conditional knockout mouse to partially delete RpS12 , which results in homozygous embryonic lethality. Rps12 +/- mice have growth and morphological defects, pancytopenia and impaired erythropoiesis. A striking reduction in hematopoietic stem cells (HSCs) and progenitors in the bone marrow (BM) was associated with decreased ability to repopulate the blood system after competitive and non-competitive BM transplantation. The mutants exhibited loss of HSC quiescence, which was associated with ERK and MTOR activation and increased global translation in HSC and progenitors. Thus, RpS12 has a very strong requirement in maintaining HSC quiescence and function, in addition to erythropoiesis that is affected in DBA patients.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220716,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"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":586699,"name":"Kristina Ames","orcid":"0000-0002-6845-0898","position":1,"is_corresponding":false},{"id":681769,"name":"Jacky Chuen","orcid":"0000-0003-4781-6907","position":2,"is_corresponding":false},{"id":586706,"name":"Kira Gritsman","orcid":"0000-0002-1367-1167","position":3,"is_corresponding":false},{"id":681771,"name":"Nicholas E. Baker","orcid":"0000-0002-4250-3488","position":4,"is_corresponding":false},{"id":820924,"name":"Virginia Folgado-Marco","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:53:50.838581Z","pmid":null,"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":[]}