ReferenceID 6349

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

Cell Mol Immunol

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. Wheth

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Reference Id
6349
Evidence Id
22939
Core Evidence Id
22939
Source Reference Id
5973
Herb2 Reference Id
HBREF006770
Subject Paper Key
HBIN046383_35301470
Pubmed Id
35301470
Doi
10.1038/s41423-022-00842-9
Paper Title
Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity
Paper 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.
Journal
Cell Mol Immunol
Publish Year
2022
Experiment Subject
mouse; human; patient
Experiment Type
Animal Experiment
Phenotype Related
Infectious Diseases; Neutropenia
Paper Title Cn
Paper Title En
Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity
Bilingual Status
semi_complete