JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal

Marianne Santaguida, Koen Schepers, Bryan King, Amit J. Sabnis, E. Camilla Forsberg, Joanne Attema, Benjamin S. Braun, Emmanuelle Passegue

Research output: Contribution to journalArticlepeer-review

97 Citations (SciVal)

Abstract

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.
Original languageEnglish
Pages (from-to)341-352
JournalCancer Cell
Volume15
Issue number4
DOIs
Publication statusPublished - 2009

Subject classification (UKÄ)

  • Cancer and Oncology

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