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Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity.
Ye, Buqing; Yang, Liuliu; Liu, Benyu; Liu, Nian; Fan, Dongdong; Li, Huimu; Sun, Lei; Du, Ying; Wang, Shuo; Tian, Yong; Fan, Zusen.
Afiliación
  • Ye B; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. bqye@pku.edu.cn.
  • Yang L; Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100080, China. bqye@pku.edu.cn.
  • Liu B; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Liu N; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Fan D; Research Center of Basic Medicine, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
  • Li H; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Sun L; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Du Y; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Wang S; Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • Tian Y; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Fan Z; Core Facility Center, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Cell Mol Immunol ; 19(5): 619-633, 2022 05.
Article en En | MEDLINE | ID: mdl-35301470
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dioxigenasas / Neutropenia Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: China
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dioxigenasas / Neutropenia Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: China