AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis
| Autor: | Seishi Ogawa, Tetsuya Yamagata, Toshiki Saito, Ieharu Yamazaki, Sachiko Seo, Shigeru Chiba, Motoshi Ichikawa, Kinuko Mitani, Mineo Kurokawa, Hisamaru Hirai, Takashi Asai, Go Yamamoto |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Myeloid Bone Marrow Cells Mice Inbred Strains Mice Transgenic Stem cell factor Biology General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Proto-Oncogene Proteins hemic and lymphatic diseases medicine Animals Humans Cell Lineage Lymphocytes Progenitor cell Cell Size Myeloid leukemia Cell Differentiation General Medicine Hematopoietic Stem Cells Hematopoiesis DNA-Binding Proteins Haematopoiesis medicine.anatomical_structure RUNX1 chemistry Core Binding Factor Alpha 2 Subunit Gene Targeting Immunology Cancer research Bone marrow Stem cell Megakaryocytes Transcription Factors |
| Zdroj: | Nature Medicine. 10:299-304 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Embryonic development of multilineage hematopoiesis requires the precisely regulated expression of lineage-specific transcription factors, including AML-1 (encoded by Runx1; also known as CBFA-2 or PEBP-2αB)1,2,3,4,5. In vitro studies and findings in human diseases, including leukemias6,7, myelodysplastic syndromes8 and familial platelet disorder with predisposition to acute myeloid leukemia (AML)9, suggest that AML-1 has a pivotal role in adult hematopoiesis. However, this role has not been fully uncovered in vivo because of the embryonic lethality of Runx1 knockout in mice. Here we assess the requirement of AML-1/Runx1 in adult hematopoiesis using an inducible gene-targeting method10. In the absence of AML-1, hematopoietic progenitors were fully maintained with normal myeloid cell development. However, AML-1-deficient bone marrow showed inhibition of megakaryocytic maturation, increased hematopoietic progenitor cells and defective T- and B-lymphocyte development. AML-1 is thus required for maturation of megakaryocytes and differentiation of T and B cells, but not for maintenance of hematopoietic stem cells (HSCs) in adult hematopoiesis. |
| Databáze: | OpenAIRE |
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