TY - JOUR
T1 - Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation
AU - Iwasaki, Hiromi
AU - Somoza, Chamorro
AU - Shigematsu, Hirokazu
AU - Duprez, Estelle A.
AU - Iwasaki-Arai, Junko
AU - Mizuno, Shin Ichi
AU - Arinobu, Yojiro
AU - Geary, Kristin
AU - Zhang, Pu
AU - Dayaram, Tajhal
AU - Fenyus, Maris L.
AU - Elf, Shannon
AU - Chan, Susan
AU - Kastner, Philippe
AU - Huettner, Claudia S.
AU - Murray, Richard
AU - Tenen, Daniel G.
AU - Akashi, Koichi
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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 myelolymphold 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 m situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphold 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 immunoglobulln 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.
AB - 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 myelolymphold 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 m situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphold 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 immunoglobulln 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.
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U2 - 10.1182/blood-2005-03-0860
DO - 10.1182/blood-2005-03-0860
M3 - Article
C2 - 15914556
AN - SCOPUS:23944446085
SN - 0006-4971
VL - 106
SP - 1590
EP - 1600
JO - Blood
JF - Blood
IS - 5
ER -