JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1400361
- author
- Santaguida, Marianne ; Schepers, Koen ; King, Bryan ; Sabnis, Amit J. ; Forsberg, E. Camilla ; Attema, Joanne LU ; Braun, Benjamin S. and Passegue, Emmanuelle
- organization
- publishing date
- 2009
- 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}}, }