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Article Dans Une Revue Blood Année : 2005

Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation.

Hiromi Iwasaki
  • Fonction : Auteur
Chamorro Somoza
  • Fonction : Auteur
Hirokazu Shigematsu
  • Fonction : Auteur
Estelle A Duprez
Junko Iwasaki-Arai
  • Fonction : Auteur
Shin-Ichi Mizuno
  • Fonction : Auteur
Yojiro Arinobu
  • Fonction : Auteur
Kristin Geary
  • Fonction : Auteur
Pu Zhang
  • Fonction : Auteur
Tajhal Dayaram
  • Fonction : Auteur
Maris L Fenyus
  • Fonction : Auteur
Shannon Elf
  • Fonction : Auteur
Claudia S Huettner
  • Fonction : Auteur
Richard M. Murray
  • Fonction : Auteur
Daniel G Tenen
  • Fonction : Auteur
Koichi Akashi
  • Fonction : Auteur

Résumé

The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent "priming" of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages.

Dates et versions

hal-00187635 , version 1 (15-11-2007)

Identifiants

Citer

Hiromi Iwasaki, Chamorro Somoza, Hirokazu Shigematsu, Estelle A Duprez, Junko Iwasaki-Arai, et al.. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation.. Blood, 2005, 106 (5), pp.1590-600. ⟨10.1182/blood-2005-03-0860⟩. ⟨hal-00187635⟩
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