Journal of Hematology & Oncology | |
Pten regulates homeostasis and inflammation-induced migration of myelocytes in zebrafish | |
Yong Zhou2  Ai-Hua Gu1  Ting-Xi Liu2  Min Deng2  Yi Chen3  Yi Jin3  Wei-Chun Li2  Mei Dong2  Lei Wang2  Hao Yuan3  Hong-Bo Fan2  Ting-Ting Du3  Dan Su2  Yu Xia2  Chun-Guang Ren2  Zhi-Wei Dong2  | |
[1] State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China;Key Laboratory of Stem Cell Biology, State Key Laboratory for Medical Genomics and Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200025, China;Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China | |
关键词: Zebrafish; Definitive myelopoiesis; Myeloid cells; cebpa; pten; | |
Others : 801823 DOI : 10.1186/1756-8722-7-17 |
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received in 2014-02-02, accepted in 2014-02-27, 发布年份 2014 | |
【 摘 要 】
Background
Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) is frequently observed in hematopoietic malignancies. Although PTEN has been implicated in maintaining the quiescence of hematopoietic stem cells (HSCs), its role in hematopoiesis during ontogeny remains largely unexplored.
Methods
The expression of hematopoietic marker genes was analyzed via whole mount in situ hybridization assay in ptena and ptenb double mutant zebrafish. The embryonic myelopoiesis was characterized by living imaging and whole mount in situ immunofluorescence with confocal microscopy, as well as cell-specific chemical staining for neutrophils and macrophages. Analyses of the involved signaling pathway were carried out by inhibitor treatment and mRNA injection.
Results
Pten-deficient zebrafish embryos exhibited a strikingly increased number of myeloid cells, which were further characterized as being immune deficient. In accordance with this finding, the inhibition of phosphoinositide 3-kinase (PI3K) or the mechanistic target of rapamycin (mTOR) corrected the expansive myelopoiesis in the pten-deficient embryos. Further mechanistic studies revealed that the expression of cebpa, a critical transcription factor in myeloid precursor cells, was downregulated in the pten-deficient myeloid cells, whereas the injection of cebpa mRNA markedly ameliorated the dysmyelopoiesis induced by the loss of pten.
Conclusions
Our data provide in vivo evidence that definitive myelopoiesis in zebrafish is critically regulated by pten via the elevation of cebpa expression.
【 授权许可】
2014 Dong et al.; licensee BioMed Central Ltd.
【 预 览 】
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