| Autor: |
Meichao Zhang, Yiling Meng, Yingxia Ying, Pingting Zhou, Suning Zhang, Yong Fang, Yuan Yao, Dong Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Death Discovery, Vol 9, Iss 1, Pp 1-11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-023-01575-y |
| Popis: |
Abstract The molecular programs that govern the directed differentiation of myeloid progenitor cells are still poorly defined. Using a previously established immortalized, phenotypically normal myeloid progenitor cell model mEB8-ER, we unveil a new mechanism mediated by STAT5 and STAT3 at a bifurcation point of myeloid progenitor cell-fate specification. We find that myeloid progenitor cells can spontaneously differentiate into neutrophils with a basal level of STAT3 phosphorylation, which is enhanced by G-CSF treatment or STAT3 over-expression, leading to elevated neutrophil differentiation. Reduced STAT3 phosphorylation caused by GM-CSF treatment, STAT3 specific inhibitor, or STAT3 depletion leads to attenuated myeloid differentiation into neutrophils, while elevating differentiation into monocytes/macrophages. In contrast, STAT5 appears to have an antagonistic function to STAT3. When activated by GM-CSF, STAT5 promotes myeloid differentiation into monocytes/macrophages but inhibits neutrophil differentiation. At the mechanistic level, GM-CSF activates STAT5 to up-regulate SOCS3, which attenuates STAT3 phosphorylation and consequently neutrophil differentiation, while enhancing monocyte/macrophage differentiation. Furthermore, inhibition of STAT5 and STAT3 in primary myeloid progenitors recapitulates the results from the mEB8-ER model. Together, our findings provide new mechanistic insights into myeloid differentiation and may prove useful for the diagnosis and treatment of diseases related to abnormal myeloid differentiation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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