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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1590-1600. Prepublished online as a Blood First Edition Paper on May 24, 2005; DOI 10.1182/blood-2005-03-0860. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2005-03-0860v1 106/5/1590    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Iwasaki, H. Articles by Akashi, K. Search for Related Content PubMed PubMed Citation Articles by Iwasaki, H. Articles by Akashi, K. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation Hiromi Iwasaki, Chamorro Somoza, Hirokazu Shigematsu, Estelle A. Duprez, Junko Iwasaki-Arai, Shin-ichi Mizuno, Yojiro Arinobu, Kristin Geary, Pu Zhang, Tajhal Dayaram, Maris L. Fenyus, Shannon Elf, Susan Chan, Philippe Kastner, Claudia S. Huettner, Richard Murray, Daniel G. Tenen, and Koichi Akashi From the Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; the Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan; Arbor Vitae, Sunnyvale, CA; Harvard Institutes of Medicine, Harvard Medical School, Boston, MA; the Institut de Genetique et de Biologie Moleculaire et Cellulaire, CEDEX, France; and EOS Biotech, South San Francisco, CA. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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