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Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
| In: | Blood, 106, 2005, 5, S. 1590-1600 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Iwasaki, Hiromi Somoza, Chamorro Shigematsu, Hirokazu Duprez, Estelle A. Iwasaki-Arai, Junko Mizuno, Shin-ichi Arinobu, Yojiro Geary, Kristin Zhang, Pu Dayaram, Tajhal Fenyus, Maris L. Elf, Shannon Chan, Susan Kastner, Philippe Huettner, Claudia S. Murray, Richard Tenen, Daniel G. Akashi, Koichi Iwasaki, Hiromi Somoza, Chamorro Shigematsu, Hirokazu Duprez, Estelle A. Iwasaki-Arai, Junko Mizuno, Shin-ichi Arinobu, Yojiro Geary, Kristin Zhang, Pu Dayaram, Tajhal Fenyus, Maris L. Elf, Shannon Chan, Susan Kastner, Philippe Huettner, Claudia S. Murray, Richard Tenen, Daniel G. Akashi, Koichi |
|---|---|
| author |
Iwasaki, Hiromi Somoza, Chamorro Shigematsu, Hirokazu Duprez, Estelle A. Iwasaki-Arai, Junko Mizuno, Shin-ichi Arinobu, Yojiro Geary, Kristin Zhang, Pu Dayaram, Tajhal Fenyus, Maris L. Elf, Shannon Chan, Susan Kastner, Philippe Huettner, Claudia S. Murray, Richard Tenen, Daniel G. Akashi, Koichi |
| spellingShingle |
Iwasaki, Hiromi Somoza, Chamorro Shigematsu, Hirokazu Duprez, Estelle A. Iwasaki-Arai, Junko Mizuno, Shin-ichi Arinobu, Yojiro Geary, Kristin Zhang, Pu Dayaram, Tajhal Fenyus, Maris L. Elf, Shannon Chan, Susan Kastner, Philippe Huettner, Claudia S. Murray, Richard Tenen, Daniel G. Akashi, Koichi Blood Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation Cell Biology Hematology Immunology Biochemistry |
| author_sort |
iwasaki, hiromi |
| spelling |
Iwasaki, Hiromi Somoza, Chamorro Shigematsu, Hirokazu Duprez, Estelle A. Iwasaki-Arai, Junko Mizuno, Shin-ichi Arinobu, Yojiro Geary, Kristin Zhang, Pu Dayaram, Tajhal Fenyus, Maris L. Elf, Shannon Chan, Susan Kastner, Philippe Huettner, Claudia S. Murray, Richard Tenen, Daniel G. Akashi, Koichi 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-03-0860 <jats:title>Abstract</jats:title><jats:p>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.</jats:p> Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation Blood |
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10.1182/blood-2005-03-0860 |
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| title |
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_unstemmed |
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_full |
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_fullStr |
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_full_unstemmed |
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_short |
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_sort |
distinctive and indispensable roles of pu.1 in maintenance of hematopoietic stem cells and their differentiation |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2005-03-0860 |
| publishDate |
2005 |
| physical |
1590-1600 |
| description |
<jats:title>Abstract</jats:title><jats:p>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.</jats:p> |
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| author | Iwasaki, Hiromi, Somoza, Chamorro, Shigematsu, Hirokazu, Duprez, Estelle A., Iwasaki-Arai, Junko, Mizuno, Shin-ichi, Arinobu, Yojiro, Geary, Kristin, Zhang, Pu, Dayaram, Tajhal, Fenyus, Maris L., Elf, Shannon, Chan, Susan, Kastner, Philippe, Huettner, Claudia S., Murray, Richard, Tenen, Daniel G., Akashi, Koichi |
| author_facet | Iwasaki, Hiromi, Somoza, Chamorro, Shigematsu, Hirokazu, Duprez, Estelle A., Iwasaki-Arai, Junko, Mizuno, Shin-ichi, Arinobu, Yojiro, Geary, Kristin, Zhang, Pu, Dayaram, Tajhal, Fenyus, Maris L., Elf, Shannon, Chan, Susan, Kastner, Philippe, Huettner, Claudia S., Murray, Richard, Tenen, Daniel G., Akashi, Koichi, Iwasaki, Hiromi, Somoza, Chamorro, Shigematsu, Hirokazu, Duprez, Estelle A., Iwasaki-Arai, Junko, Mizuno, Shin-ichi, Arinobu, Yojiro, Geary, Kristin, Zhang, Pu, Dayaram, Tajhal, Fenyus, Maris L., Elf, Shannon, Chan, Susan, Kastner, Philippe, Huettner, Claudia S., Murray, Richard, Tenen, Daniel G., Akashi, Koichi |
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| description | <jats:title>Abstract</jats:title><jats:p>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.</jats:p> |
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| imprint | American Society of Hematology, 2005 |
| imprint_str_mv | American Society of Hematology, 2005 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Iwasaki, Hiromi Somoza, Chamorro Shigematsu, Hirokazu Duprez, Estelle A. Iwasaki-Arai, Junko Mizuno, Shin-ichi Arinobu, Yojiro Geary, Kristin Zhang, Pu Dayaram, Tajhal Fenyus, Maris L. Elf, Shannon Chan, Susan Kastner, Philippe Huettner, Claudia S. Murray, Richard Tenen, Daniel G. Akashi, Koichi 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2005-03-0860 <jats:title>Abstract</jats:title><jats:p>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.</jats:p> Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation Blood |
| spellingShingle | Iwasaki, Hiromi, Somoza, Chamorro, Shigematsu, Hirokazu, Duprez, Estelle A., Iwasaki-Arai, Junko, Mizuno, Shin-ichi, Arinobu, Yojiro, Geary, Kristin, Zhang, Pu, Dayaram, Tajhal, Fenyus, Maris L., Elf, Shannon, Chan, Susan, Kastner, Philippe, Huettner, Claudia S., Murray, Richard, Tenen, Daniel G., Akashi, Koichi, Blood, Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_full | Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_fullStr | Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_full_unstemmed | Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_short | Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_sort | distinctive and indispensable roles of pu.1 in maintenance of hematopoietic stem cells and their differentiation |
| title_unstemmed | Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2005-03-0860 |