期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 19, 期 5, 页码 619-633出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-022-00842-9
关键词
Fibroblasts; Neutrophils; Thymidine; Transdifferentiation; Tet3
类别
资金
- National Key R&D Program of China [2020YFA0803501, 2019YFA0508501, 2021YFF0702802]
- National Natural Science Foundation of China [82130088, 31930036, 81921003, 31871494, 92042302, 91940305, 32070533, 81772646]
- Beijing Natural Science Foundation [5192018]
- Biological Resources Program of Chinese Academy of Sciences [KFJ-BRP-017]
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDB19030203]
This study demonstrates that thymidine can induce transdifferentiation of mouse fibroblasts into neutrophils, which exhibit antibacterial effects and can cure neutropenia in mice.
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 Cebp delta 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
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