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

Santaguida, Marianne ; Schepers, Koen ; King, Bryan ; Sabnis, Amit J. ; Forsberg, E. Camilla ; Attema, Joanne LU ; Braun, Benjamin S. and Passegue, Emmanuelle (2009) In Cancer Cell 15(4). p.341-352
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
15
issue
4
pages
341 - 352
publisher
Cell Press
external identifiers
  • wos:000265114200013
  • scopus:63249095562
ISSN
1878-3686
DOI
10.1016/j.ccr.2009.02.016
language
English
LU publication?
yes
id
71e7a551-6b72-4222-9efa-82660fb5697f (old id 1400361)
date added to LUP
2016-04-01 11:59:47
date last changed
2022-01-26 21:17:20
@article{71e7a551-6b72-4222-9efa-82660fb5697f,
  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.}},
  author       = {{Santaguida, Marianne and Schepers, Koen and King, Bryan and Sabnis, Amit J. and Forsberg, E. Camilla and Attema, Joanne and Braun, Benjamin S. and Passegue, Emmanuelle}},
  issn         = {{1878-3686}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{341--352}},
  publisher    = {{Cell Press}},
  series       = {{Cancer Cell}},
  title        = {{JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal}},
  url          = {{http://dx.doi.org/10.1016/j.ccr.2009.02.016}},
  doi          = {{10.1016/j.ccr.2009.02.016}},
  volume       = {{15}},
  year         = {{2009}},
}