Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence (Articolo in rivista)

Type
Label
  • Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.stem.2008.03.004 (literal)
Alternative label
  • Francesca Ficara, Mark J. Murphy, Min Lin, Michael L. Cleary (2008)
    Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence
    in Cell stem cell (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Francesca Ficara, Mark J. Murphy, Min Lin, Michael L. Cleary (literal)
Pagina inizio
  • 484 (literal)
Pagina fine
  • 496 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 2 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 5 (literal)
Note
  • Google Scholar (literal)
  • PubMe (literal)
  • ISI Web of Science (WOS) (literal)
  • Scopus (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA (literal)
Titolo
  • Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence (literal)
Abstract
  • Self-renewal is a defining characteristic of stem cells; however, the molecular pathways underlying its regulation are poorly understood. Here, we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell-cycle regulators, normally expressed in non-self-renewing multipotent progenitors. A significant proportion of Pbx1-dependent genes is associated with the TGF-? pathway, which serves a major role in maintaining HSC quiescence. Prospectively isolated, Pbx1-deficient LT-HSCs display altered transcriptional responses to TGF-? stimulation in vitro, suggesting a possible mechanism through which Pbx1 maintenance of stem cell quiescence may in part be achieved. (literal)
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