{"doi":"10.1242/dev.149419","title":"Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation. The use of inducible Runx1 expression combined with alterations in the expression of the RUNX1 co-factor CBFβ allowed us to evaluate a wide range of RUNX1 levels. We demonstrate that low RUNX1 levels are sufficient and necessary to initiate an effective endothelial-to-hematopoietic transition. Subsequently, RUNX1 is also required to complete the endothelial-to-hematopoietic transition and to generate functional hematopoietic precursors. In contrast, elevated levels of RUNX1 are able to drive an accelerated endothelial-to-hematopoietic transition, but the resulting cells are unable to generate mature hematopoietic cells. Together, our results suggest that RUNX1 dosage plays a pivotal role in hemogenic endothelium maturation and the establishment of the hematopoietic system.</jats:p>","journal":"Development","year":2018,"id":634532,"datarank":0.5983476069846413,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":0.0,"self_endowment_contribution":0.5983476069846413,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1645741,"name":"Elli Marinopoulou","orcid":null,"position":1,"is_corresponding":false},{"id":29456,"name":"Andrew J. Lilly","orcid":null,"position":2,"is_corresponding":false},{"id":1645742,"name":"Mairi Challinor","orcid":null,"position":3,"is_corresponding":false},{"id":1645743,"name":"Rahima Patel","orcid":null,"position":4,"is_corresponding":false},{"id":1645744,"name":"Christophe Lancrin","orcid":null,"position":5,"is_corresponding":false},{"id":29465,"name":"Valérie Kouskoff","orcid":"0000-0001-9801-4993","position":6,"is_corresponding":false},{"id":1391521,"name":"Georges Lacaud","orcid":"0000-0002-5630-2417","position":7,"is_corresponding":false},{"id":1645740,"name":"Michael Lie-A-Ling","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation. The use of inducible Runx1 expression combined with alterations in the expression of the RUNX1 co-factor CBFβ allowed us to evaluate a wide range of RUNX1 levels. We demonstrate that low RUNX1 levels are sufficient and necessary to initiate an effective endothelial-to-hematopoietic transition. Subsequently, RUNX1 is also required to complete the endothelial-to-hematopoietic transition and to generate functional hematopoietic precursors. In contrast, elevated levels of RUNX1 are able to drive an accelerated endothelial-to-hematopoietic transition, but the resulting cells are unable to generate mature hematopoietic cells. Together, our results suggest that RUNX1 dosage plays a pivotal role in hemogenic endothelium maturation and the establishment of the hematopoietic system.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29530939","pmcid":"PMC5868988","openalex_id":null,"authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"MR/P000673/1","title":"DECIPHERING THE BIOLOGICAL CHARACTERISTICS OF HUMAN HAEMOGENIC ENDOTHELIUM"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/I001794/1","title":"Establishment of the haemopoietic transcriptional programme: From systems approaches to molecular mechanisms"},{"funder_name":"Bloodwise","grant_id":"12037","title":null},{"funder_name":"Horizon 2020","grant_id":"GA6586250","title":null},{"funder_name":"Cancer Research UK","grant_id":"C5759/A20971","title":null},{"funder_name":"Cancer Research UK","grant_id":"12487","title":null},{"funder_name":"Cancer Research UK","grant_id":"19565","title":null},{"funder_name":"Cancer Research UK","grant_id":"12486","title":null},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":10,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1242/dev.149419","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1242/dev.149419","host_type":"publisher"},{"url":"https://journals.biologists.com/dev/article-pdf/doi/10.1242/dev.149419/3477161/dev149419.pdf","host_type":"publisher"},{"url":"https://research.manchester.ac.uk/en/publications/398d09dc-3795-4a92-be39-e51ff1440044","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5868988","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5868988","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5868988","host_type":"Europe_PMC"},{"url":"https://dev.biologists.org/content/develop/145/5/dev149419.full.pdf","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/29530939","host_type":""},{"url":"http://dx.doi.org/10.1242/dev.149419","host_type":""},{"url":"https://dx.doi.org/10.1242/dev.149419","host_type":""},{"url":"https://www.scopus.com/pages/publications/85044322800","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Endothelium, Vascular","Hematopoietic Stem Cells","Cells, Cultured","Animals","Mice, Knockout","Mice","Cell Differentiation","Hematopoiesis","Gene Expression Regulation","Gene Dosage","Core Binding Factor Alpha 2 Subunit","Hemangioblasts"],"keywords":["Dosage","Runx1","Hemogenic Endothelium","Sox7","Eht","Cbfβ","Mice, Knockout","Manchester Cancer Research Centre","Hemangioblasts","Gene Dosage","Cell Differentiation","Stem Cells and Regeneration","Hematopoietic Stem Cells","ResearchInstitutes_Networks_Beacons/mcrc; name=Manchester Cancer Research Centre","Hematopoiesis","Mice","Gene Expression Regulation","Core Binding Factor Alpha 2 Subunit","Animals","Endothelium, Vascular","Cells, Cultured"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:47:59.726106Z","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":[]}