Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity.

Buqing Ye, Liuliu Yang, Benyu Liu, Nian Liu, Dongdong Fan, Huimu Li, Lei Sun, Ying Du, Shuo Wang, Yong Tian, Zusen Fan

Cellular & molecular immunology 2022 May

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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. © 2022. The Author(s), under exclusive licence to CSI and USTC.

Citation

Buqing Ye, Liuliu Yang, Benyu Liu, Nian Liu, Dongdong Fan, Huimu Li, Lei Sun, Ying Du, Shuo Wang, Yong Tian, Zusen Fan. Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity. Cellular & molecular immunology. 2022 May;19(5):619-633