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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Hong Qian
  • Natalija Buza-Vidas
  • Craig D Hyland
  • Christina Jensen
  • Jennifer Antonchuk
  • Robert Månsson
  • Lina Thorén
  • Marja Ekblom
  • Warren S Alexander
  • Sten Eirik W Jacobsen
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology
Original languageEnglish
Pages (from-to)671-684
JournalCell Stem Cell
Volume1
Issue number6
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes