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.Whethe...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.展开更多
The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.Wh...The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.While tet(X4)was not identified in our samples,tet(X3)was found in two gut microbiomes of bird fecal samples,with 100%amino acid identity of sites 150–387.These results suggest that tet(X3)has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.展开更多
基金supported by the National Key R&D Program of China (2020YFA0803501,2019YFA0508501,2021YFF0702802)the National Natural Science Foundation of China (82130088,31930036,81921003,31871494,92042302,91940305,32070533,81772646)+2 种基金the Beijing Natural Science Foundation (5192018)the Biological Resources Program of Chinese Academy of Sciences (KFJ-BRP-017)the Strategic Priority Research Programs of the Chinese Academy of Sciences (XDB19030203).
文摘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.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS,XDB29010202)the External Cooperation Program of CAS(153211KYSB20160001).
文摘The emergence of mobile Tigecycline-resistant tet(X3)and tet(X4)is believed to be a global threat to public health.Here,we investigated the prevalence of tet(X3)and tet(X4)in our metagenomic data of migratory birds.While tet(X4)was not identified in our samples,tet(X3)was found in two gut microbiomes of bird fecal samples,with 100%amino acid identity of sites 150–387.These results suggest that tet(X3)has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.
