title: miR-142-3p acts as an essential modulator of neutrophil development in zebrafish.
abstract: Neutrophils play critical roles in vertebrate innate immune responses. As an emerging regulator in normal myelopoiesis, the precise roles of microRNA in the development of neutrophils have yet to be clarified. Using zinc-finger nucleases, we have successfully generated heritable mutations in miR-142a and miR-142b and showed that hematopoietic-specific miR-142-3p is completely deleted in miR-142 double mutant zebrafish. The lack of miR-142-3p resulted in aberrant reduction and hypermaturation of neutrophils in definitive myelopoiesis, as well as impaired inflammatory migration of neutrophils in the fetal stage. Furthermore, the adult myelopoiesis in the miR-142-3p-deficient zebrafish was also affected, producing irregular hypermature neutrophils with increased cell size and a decreased nucleocytoplasmic ratio. Additionally, miR-142-3p-deficient zebrafish are expected to develop a chronic failure of myelopoiesis with age. Transcriptome analysis showed an aberrant activation of the interferon γ (IFN-γ) signaling pathway in myelomonocytes after miR-142-3p deletion. We found that the reduced number and hypermaturation of neutrophils caused by loss of miR-142-3p was mainly mediated by the abnormally activated IFN-γ signaling, especially the upregulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Fan
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China; and.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Du
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Zhao-Zheng
authors.initials: ZZ
authors.lastname: Meng
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Huang-Tian
authors.initials: HT
authors.lastname: Yang
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Qing
authors.initials: Q
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Gu
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Ting-Xi
authors.initials: TX
authors.lastname: Liu
authors.affiliation: Key Laboratory of Stem Cell Biology and State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017353:Gene Deletion; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D038042:Myelopoiesis / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D059467:Transcriptome; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D050856:Interferon Regulatory Factor-1; C577490:MIRN142 microRNA, zebrafish; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; D029961:Zebrafish Proteins; C494083:stat1a protein, zebrafish; D007371:Interferon-gamma