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While the current therapy, such as granulocyte colony\u2010stimulating factor (G\u2010CSF), boosts neutrophil counts, its late\u2010stage action mobilizes dysfunctional cells, underscoring the need for early\u2010lineage therapeutic interventions. Leveraging zebrafish models, we found that transcriptional enhanced associate domain 1a (TEAD1a) initiates transcriptional priming to govern neutrophil lineage specification preceding hematopoietic stem cell formation. Genetic ablation of TEAD1a or disruption of its interaction with Yes\u2010associated protein 1 (YAP1) induces profound neutropenia. Mechanistic interrogation reveals that TEAD1a\/YAP1 complexes potentiate Notch1\u2010mediated signaling to activate a Spi1\/Cebp\u03b1 transcriptional cascade during myeloid progenitor specification. This study uncovers a novel developmental regulatory window for myeloid lineage commitment and demonstrates the evolutionarily conserved role of TEAD1a\u2010mediated transcriptional priming in orchestrating neutrophil development. The discovery of this ultra\u2010early regulatory node provides a molecularly defined target for generating developmentally competent neutrophils, offering an innovative therapeutic strategy for refractory neutropenia.<\/jats:p>","DOI":"10.1002\/advs.202505441","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T13:45:28Z","timestamp":1756388728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tead1a Initiates Transcriptional Priming Through the TEAD1a\/YAP\u2010Notch1\u2010Spi1\/Cebp\u03b1 Axis to Promote Neutrophil Fate"],"prefix":"10.1002","volume":"12","author":[{"given":"Wang","family":"Yiqin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou First People's Hospital the Second Affiliated Hospital of South China University of Technology Guangzhou 510080 China"},{"name":"Center for Medical Research on Innovation and Translation Guangzhou First People's Hospital School of Medicine South China University of Technology Guangzhou 510080 China"},{"name":"CNRS\u2010LIA Hematology and Cancer Sino\u2010French Research Center for Life Sciences and Genomics State Key Laboratory of Medical Genomics Rui\u2010Jin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ruimeng","sequence":"additional","affiliation":[{"name":"CNRS\u2010LIA Hematology and Cancer Sino\u2010French Research Center for Life Sciences and Genomics State Key Laboratory of Medical Genomics Rui\u2010Jin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Peihong","sequence":"additional","affiliation":[{"name":"Department of Hematology Guangzhou First People's Hospital School of Medicine South China University of Technology Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Xiaohui","sequence":"additional","affiliation":[{"name":"CNRS\u2010LIA Hematology and Cancer Sino\u2010French Research Center for Life Sciences and Genomics State Key Laboratory of Medical Genomics Rui\u2010Jin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hao","sequence":"additional","affiliation":[{"name":"CNRS\u2010LIA Hematology and Cancer Sino\u2010French Research Center for Life Sciences and Genomics State Key Laboratory of Medical Genomics Rui\u2010Jin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Hongli","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou First People's Hospital the Second Affiliated Hospital of South China University of Technology Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Yongjian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Guangzhou First People's Hospital the Second Affiliated Hospital of South China University of Technology Guangzhou 510080 China"},{"name":"Center for Medical Research on Innovation and Translation Guangzhou First People's Hospital School of Medicine South China University of Technology Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-5341","authenticated-orcid":false,"given":"Xie","family":"Baoshu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Sun Yat\u2010sen University Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2921"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012073432307"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2023.108476"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2227-7"},{"key":"e_1_2_9_5_1","first-page":"1027","volume":"11","author":"Sugden W. 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