IFN-I-Mediated Transcriptional Reprogramming Drives Myeloid-Skewed Hematopoiesis in Sickle Cell Anemia - PubMed
7 hours ago
- #IFN-I signaling
- #sickle cell anemia
- #myelopoiesis
- Neutrophils and monocytes are persistently elevated in sickle cell anemia (SCA).
- Hematopoietic stem and multipotent progenitor cells (HSPCs) in SCA are transcriptionally reprogrammed toward myeloid differentiation.
- Type I interferon (IFN-I) signaling is aberrantly activated, promoting premature myeloid commitment of hematopoietic stem cells.
- SCA progenitors show unexpected responsiveness to granulocyte colony-stimulating factor (G-CSF) through upregulation of CSF3R, leading to skewed myelopoiesis toward the monocytic lineage.
- Hydroxyurea treatment attenuates IFN-I signaling in neutrophils, reducing excessive inflammation and granulopoiesis.
- IFN-I-driven remodeling of hematopoiesis is identified as a fundamental mechanism of leukocytosis and chronic inflammation in SCA.