{"doi":"10.1016/j.celrep.2022.110881","title":"Differential Etv2 threshold requirement for endothelial and erythropoietic development","abstract":"Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages.","journal":"Cell Reports","year":2022,"id":251851,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":895785,"name":"Kelly Lammerts van Bueren","orcid":null,"position":1,"is_corresponding":false},{"id":37345,"name":"Diane E. Dickel","orcid":"0000-0001-5497-6824","position":2,"is_corresponding":false},{"id":488444,"name":"Ivana Zlatanova","orcid":"0000-0002-7911-2843","position":3,"is_corresponding":false},{"id":71688,"name":"Reuben Thomas","orcid":"0000-0003-3176-7303","position":4,"is_corresponding":false},{"id":251030,"name":"Carlos O. Lizama","orcid":"0000-0002-0471-8525","position":5,"is_corresponding":false},{"id":895786,"name":"Shan-Mei Xu","orcid":null,"position":6,"is_corresponding":false},{"id":895286,"name":"Ann C. Zovein","orcid":"0000-0003-3298-7308","position":7,"is_corresponding":false},{"id":23359,"name":"Kohta Ikegami","orcid":"0000-0002-0405-1193","position":8,"is_corresponding":false},{"id":270583,"name":"Ivan P. Moskowitz","orcid":"0000-0003-0014-4963","position":9,"is_corresponding":false},{"id":21361,"name":"Katherine S. Pollard","orcid":"0000-0002-9870-6196","position":10,"is_corresponding":false},{"id":43118,"name":"Len A. Pennacchio","orcid":"0000-0002-8748-3732","position":11,"is_corresponding":false},{"id":316851,"name":"Brian L. Black","orcid":"0000-0002-6664-8913","position":12,"is_corresponding":false},{"id":316846,"name":"Tanvi Sinha","orcid":"0000-0001-9509-5687","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T00:24:41.993282Z","pmid":"35649376","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":[]}