期刊
CANCER CELL
卷 15, 期 4, 页码 341-352出版社
CELL PRESS
DOI: 10.1016/j.ccr.2009.02.016
关键词
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资金
- Fonds de la recherche en sante du Quebec
- Netherlands Organisation for Scientific Research (NWO)
- Dutch Cancer Society (KWF).
- Concern Foundation
- UCSF Research Evaluation and Allocation Committee
- NIH [HL092471]
Loss of the JunB/AP-1 transcription factor induces a myeloproliferative disease (MPD) arising from the hematopoietic stem cell (HSC) compartment. Here, we show that junB inactivation deregulates the cell-cycle machinery and increases the proliferation of long-term repopulating HSCs (LT-HSCs) without impairing their self-renewal or regenerative potential in vivo. We found that JunB loss destabilizes a complex network of genes and pathways that normally limit myeloid differentiation, leading to impaired responsiveness to both Notch and TGF-beta signaling due in part to transcriptional deregulation of the Hes1 gene. These results demonstrate that LT-HSC proliferation and differentiation are uncoupled from self-renewal and establish some of the mechanisms by which JunB normally limits the production of myeloid progenitors, hence preventing initiation of myeloid malignancies.
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