Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. - Archive ouverte HAL Access content directly
Journal Articles Blood Year : 2005

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

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

Abstract

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 and versions

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

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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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