title: Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells.
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.
authors: Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84, Sweden.
authors: Hong
authors: H
authors: Qian
authors: Natalija
authors: N
authors: Buza-Vidas
authors: Craig D
authors: CD
authors: Hyland
authors: Christina T
authors: CT
authors: Jensen
authors: Jennifer
authors: J
authors: Antonchuk
authors: Robert
authors: R
authors: Månsson
authors: Lina A
authors: LA
authors: Thoren
authors: Marja
authors: M
authors: Ekblom
authors: Warren S
authors: WS
authors: Alexander
authors: Sten Eirik W
authors: SE
authors: Jacobsen
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D013926:Thrombopoietin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
chemical_list: D013926:Thrombopoietin