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Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells.

Qian, Hong LU ; Buza-Vidas, Natalija LU ; Hyland, Craig D; Jensen, Christina LU ; Antonchuk, Jennifer LU ; Månsson, Robert LU ; Thorén, Lina LU ; Ekblom, Marja LU ; Alexander, Warren S and Jacobsen, Sten Eirik W LU (2007) In Cell Stem Cell 1(6). p.671-684
Abstract
The role of cytokines in regulation of hematopoietic stem cells (HSCs) remains poorly understood. Herein we demonstrate that thrombopoietin (THPO) and its receptor, MPL, are critically involved in postnatal steady-state HSC maintenance, reflected in a 150-fold reduction of HSCs in adult Thpo(-/-) mice. Further, whereas THPO and MPL proved not required for fetal HSC expansion, HSC expansion posttransplantation was highly MPL and THPO dependent. The distinct role of THPO in postnatal HSC maintenance is accompanied by accelerated HSC cell-cycle kinetics in Thpo(-/-) mice and reduced expression of the cyclin-dependent kinase inhibitors p57(Kip2) and p19(INK4D) as well as multiple Hox transcription factors. Although also predicted to be an HSC... (More)
The role of cytokines in regulation of hematopoietic stem cells (HSCs) remains poorly understood. Herein we demonstrate that thrombopoietin (THPO) and its receptor, MPL, are critically involved in postnatal steady-state HSC maintenance, reflected in a 150-fold reduction of HSCs in adult Thpo(-/-) mice. Further, whereas THPO and MPL proved not required for fetal HSC expansion, HSC expansion posttransplantation was highly MPL and THPO dependent. The distinct role of THPO in postnatal HSC maintenance is accompanied by accelerated HSC cell-cycle kinetics in Thpo(-/-) mice and reduced expression of the cyclin-dependent kinase inhibitors p57(Kip2) and p19(INK4D) as well as multiple Hox transcription factors. Although also predicted to be an HSC viability factor, BCL2 failed to rescue the HSC deficiency of Thpo(-/-) mice. Thus, THPO regulates posttransplantation HSC expansion as well as the maintenance of adult quiescent HSCs, of critical importance to avoid postnatal HSC exhaustion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Stem Cell
volume
1
issue
6
pages
671 - 684
publisher
Cell Press
external identifiers
  • pmid:18371408
  • wos:000251784300013
  • scopus:36749001043
ISSN
1934-5909
DOI
10.1016/j.stem.2007.10.008
language
English
LU publication?
yes
id
01eae5ba-0baf-448e-b1ba-d24a5276c975 (old id 1052048)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18371408?dopt=Abstract
date added to LUP
2008-04-02 16:44:03
date last changed
2017-11-19 03:34:44
@article{01eae5ba-0baf-448e-b1ba-d24a5276c975,
  abstract     = {The role of cytokines in regulation of hematopoietic stem cells (HSCs) remains poorly understood. Herein we demonstrate that thrombopoietin (THPO) and its receptor, MPL, are critically involved in postnatal steady-state HSC maintenance, reflected in a 150-fold reduction of HSCs in adult Thpo(-/-) mice. Further, whereas THPO and MPL proved not required for fetal HSC expansion, HSC expansion posttransplantation was highly MPL and THPO dependent. The distinct role of THPO in postnatal HSC maintenance is accompanied by accelerated HSC cell-cycle kinetics in Thpo(-/-) mice and reduced expression of the cyclin-dependent kinase inhibitors p57(Kip2) and p19(INK4D) as well as multiple Hox transcription factors. Although also predicted to be an HSC viability factor, BCL2 failed to rescue the HSC deficiency of Thpo(-/-) mice. Thus, THPO regulates posttransplantation HSC expansion as well as the maintenance of adult quiescent HSCs, of critical importance to avoid postnatal HSC exhaustion.},
  author       = {Qian, Hong and Buza-Vidas, Natalija and Hyland, Craig D and Jensen, Christina and Antonchuk, Jennifer and Månsson, Robert and Thorén, Lina and Ekblom, Marja and Alexander, Warren S and Jacobsen, Sten Eirik W},
  issn         = {1934-5909},
  language     = {eng},
  number       = {6},
  pages        = {671--684},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells.},
  url          = {http://dx.doi.org/10.1016/j.stem.2007.10.008},
  volume       = {1},
  year         = {2007},
}