| Literature DB >> 35301470 |
Buqing Ye1,2, Liuliu Yang3, Benyu Liu3,4, Nian Liu3,5, Dongdong Fan6, Huimu Li3,5, Lei Sun7, Ying Du3, Shuo Wang3, Yong Tian8,9, Zusen Fan10,11.
Abstract
Neutrophils are derived from bone marrow hematopoietic stem cells (HSCs) and are the largest population among circulating white blood cells in humans, acting as the first line of defense against invading pathogens. Whether neutrophils can be generated by transdifferentiation strategies is unknown. Here, we show that thymidine induces the conversion of mouse fibroblasts to neutrophils. Induced neutrophils (iNeus) showed antibacterial effects and did not undergo malignant transformation in vivo. Importantly, iNeu transplantation cured neutropenia in mice in vivo. Mechanistically, thymidine mediates iNeu conversion by enhancing Tet3 activity. Tet3 initiates the expression of the neutrophil fate decision factors Cebpδ and Rfx1 that drive the transdifferentiation of mouse fibroblasts to neutrophils. Therefore, the induction of functional neutrophils by chemicals may provide a potential therapeutic strategy for patients with neutropenia patients and infectious diseases.Fibroblasts; Neutrophils; Thymidine; Transdifferentiation; Tet3.Entities:
Keywords: Fibroblasts; Neutrophils; Tet3; Thymidine; Transdifferentiation
Mesh：
Substances：
Year: 2022 PMID： 35301470 PMCID： PMC9061759 DOI： 10.1038/s41423-022-00842-9
Source DB: PubMed Journal: Cell Mol Immunol ISSN： 1672-7681 Impact factor: 22.096