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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
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
2009-06-15 14:36:12
date last changed
2017-08-27 04:00:00
@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},
  volume       = {15},
  year         = {2009},
}