Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells...Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor sites.Neutrophil involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and progression.Studies have indicated both pro-and anti-tumor properties of infiltrating neutrophils.The TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory response.In contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T cells.Here,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.展开更多
Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation,which is crucial for maintaining homeostasis.Acute infections can prompt a hematopoietic response kn...Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation,which is crucial for maintaining homeostasis.Acute infections can prompt a hematopoietic response known as emergency myelopoiesis.In this study,using a Candida albicans(C.albicans)infection model,we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates.Impaired myeloid hematopoiesis and immune cell production were evident,as proved by the decreased numbers of hematopoietic stem and progenitor cells(HSPCs)and granulocytes in the bone marrow of Fhl2-deficient mice.In conclusion,FHL2 regulated emergency myelopoiesis in response to C.albicans,affecting the host’s defense against pathogens.展开更多
Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and...Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naive to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naive–primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naive–primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naive versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naive–primed state conversion of ES cells, which is partially mediated by a Lin28a–let-7–Dnmt3a/b–Dppa3 axis.展开更多
基金A.Y.H. was supported by NRSA Institutional Postdoctoral Training grant T32 (Grant No. 5T32HL066987-20)C.S. was supported by grants from the National Natural Science Foundation of China (Grant No. 82001661)+1 种基金F.X.M. and C.S. were supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund (Grant No. HH22KYZX0019)F.X.M. was supported by the National Natural Science Foundation of China (Grant No. 82171756)
文摘Neutrophils play an essential role in the defense against bacterial infections and orchestrate both the innate and adaptive immune responses.With their abundant numbers,diverse function and short life span,these cells are at the forefront of immune responses,and have gained attention in recent years because of their presence in tumor sites.Neutrophil involvement pertains to tumor cells'ability to construct a suitable tumor microenvironment(TME)that accelerates their own growth and malignancy,by facilitating their interaction with surrounding cells through the circulatory and lymphatic systems,thereby influencing tumor development and progression.Studies have indicated both pro-and anti-tumor properties of infiltrating neutrophils.The TME can exploit neutrophil function,recruitment,and even production,thus resulting in pro-tumor properties of neutrophils,including promotion of genetic instability,tumor cell proliferation,angiogenesis and suppression of anti-tumor or inflammatory response.In contrast,neutrophils can mediate anti-tumor resistance by direct cytotoxicity to the tumor cells or by facilitating anti-tumor functions via crosstalk with T cells.Here,we summarize current knowledge regarding the effects of neutrophil heterogeneity under homeostatic and tumor conditions,including neutrophil phenotype and function,in cancer biology.
基金supported by the National Key Research and Development Program of China(2020YFE0203000,2021YFA1100900)the National Natural Science Foundation of China(92368202,82270120)+2 种基金the Haihe Laboratory of Cell Ecosystem Innovation Fund(22HHXBSS00016)the CAMS Initiative for Innovative Medicine(2021-I2M-1-019,2022-I2M-2-001)the CAMS Fundamental Research Funds for Central Research Institutes(3332021093).
文摘Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation,which is crucial for maintaining homeostasis.Acute infections can prompt a hematopoietic response known as emergency myelopoiesis.In this study,using a Candida albicans(C.albicans)infection model,we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates.Impaired myeloid hematopoiesis and immune cell production were evident,as proved by the decreased numbers of hematopoietic stem and progenitor cells(HSPCs)and granulocytes in the bone marrow of Fhl2-deficient mice.In conclusion,FHL2 regulated emergency myelopoiesis in response to C.albicans,affecting the host’s defense against pathogens.
基金the National Natural Science Foundation of China (31771636, 81671734, and 81501528)National Key R&D Plan (2017YFA0103201 and 2011DAV00088)+2 种基金Tianjin Natural Science Foundation (18JCYBJC24400)CAMS Initiative for Innovative Medicine (CAMS-12M 2016-12M-1-017)Program for Changjiang Scholars and Innovative Research Team in University (IRT13023).
文摘Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naive to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naive–primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naive–primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naive versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naive–primed state conversion of ES cells, which is partially mediated by a Lin28a–let-7–Dnmt3a/b–Dppa3 axis.
