{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:06:27Z","timestamp":1792069587992,"version":"4.4.0"},"posted":{"date-parts":[[2025,10,7]]},"group-title":"In Review","reference-count":55,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,2]]},"abstract":"<title>Abstract<\/title>\n        <p>Neutrophils and monocytes are persistently elevated in sickle cell anemia (SCA), yet the intrinsic mechanisms driving pathological myelopoiesis and inflammation remain poorly defined. Through single-cell RNA sequencing and functional assays, we demonstrate that hematopoietic stem and multipotent progenitor cells (HSPCs) in SCA are transcriptionally reprogrammed toward myeloid differentiation. This process is orchestrated by aberrant activation of type I interferon (IFN-I) signaling, which promotes premature myeloid commitment of hematopoietic stem cells. SCA progenitors further exhibit unexpected responsiveness to granulocyte colony-stimulating factor (G-CSF) through upregulation of CSF3R, resulting in skewed myelopoiesis toward the monocytic lineage. Importantly, hydroxyurea treatment attenuates IFN-I signaling in neutrophils, consistent with its therapeutic role in reducing excessive inflammation and granulopoiesis. Collectively, these findings uncover IFN-I\u2013driven remodeling of hematopoiesis as a fundamental mechanism of leukocytosis and chronic inflammation in SCA, and establish a tractable therapeutic axis to mitigate innate immunity activation in this disease.<\/p>","DOI":"10.21203\/rs.3.rs-7766748\/v1","type":"posted-content","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T08:38:20Z","timestamp":1759826300000},"source":"Crossref","is-referenced-by-count":1,"title":["IFN-I-Mediated Transcriptional Reprogramming Drives Myeloid-skewed Hematopoiesis in Sickle Cell Anemia"],"prefix":"10.21203","author":[{"given":"Marion","family":"Serra","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Aglave","sequence":"additional","affiliation":[{"name":"Gustave Roussy, Plateforme de bioinformatique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Salma","sequence":"additional","affiliation":[{"name":"IGMM, Univ Montpellier, CNRS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Akkaya","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Hermand","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Lefevre","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Duval","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, EFS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Merrer","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Epid\u00e9miologie Clinique, INSERM CIC 1426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fallou","family":"Leye","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019Epid\u00e9miologie Clinique, INSERM CIC 1426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Magne","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Plo","sequence":"additional","affiliation":[{"name":"Inserm UMR 1287, Universit\u00e9 Paris Saclay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Blanc","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Soler","sequence":"additional","affiliation":[{"name":"IGMM, Univ Montpellier, CNRS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slim","family":"Azouzi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM, EFS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berengere","family":"Koehl","sequence":"additional","affiliation":[{"name":"Sickle Cell Disease Center, Hematology Unit, H\u00f4pital Robert Debr\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle Cell Disease","volume":"376","author":"Piel FB","year":"2017","unstructured":"Piel FB, Steinberg MH, Rees DC (2017) Sickle Cell Disease. 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