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

In English

Författare

  • 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

Summary, in English

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.

Publiceringsår

2007

Språk

Engelska

Sidor

671-684

Publikation/Tidskrift/Serie

Cell Stem Cell

Volym

1

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

Cell Press

Ämne

  • Cell Biology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1934-5909