Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity.
Cell Mol Immunol
; 19(5): 619-633, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35301470
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dioxigenases
/
Neutropenia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Mol Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China