PUBLICATION
miR-142-3p acts as an essential modulator of neutrophil development in zebrafish
- Authors
- Fan, H.B., Liu, Y.J., Wang, L., Du, T.T., Dong, M., Gao, L., Meng, Z.Z., Jin, Y., Chen, Y., Deng, M., Yang, H.T., Jing, Q., Gu, A.H., Liu, T.X., Zhou, Y.
- ID
- ZDB-PUB-140706-13
- Date
- 2014
- Source
- Blood 124(8): 1320-30 (Journal)
- Registered Authors
- Chen, Yi, Dong, Mei, Jin, Yi, Liu, Ting Xi, Zhou, Yong
- Keywords
- none
- Datasets
- GEO:GSE58944
- MeSH Terms
-
- Animals
- Gene Deletion
- Interferon Regulatory Factor-1/genetics
- Interferon Regulatory Factor-1/metabolism
- Interferon-gamma/genetics
- Interferon-gamma/metabolism
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Myelopoiesis/physiology*
- Neutrophils/cytology
- Neutrophils/metabolism*
- STAT1 Transcription Factor/genetics
- STAT1 Transcription Factor/metabolism
- Signal Transduction/physiology*
- Transcriptome
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 24990885 Full text @ Blood
Citation
Fan, H.B., Liu, Y.J., Wang, L., Du, T.T., Dong, M., Gao, L., Meng, Z.Z., Jin, Y., Chen, Y., Deng, M., Yang, H.T., Jing, Q., Gu, A.H., Liu, T.X., Zhou, Y. (2014) miR-142-3p acts as an essential modulator of neutrophil development in zebrafish. Blood. 124(8):1320-30.
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 gamma signalling 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 IFNγ signalling, especially the up-regulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping