Open AccessEnforced Expression of PU.1 Rescues Osteoclastogenesis from Embryonic Stem Cells Lacking Tal‐1
Author(s) -
Tsuneto Motokazu,
Tominaga Akira,
Yamazaki Hidetoshi,
Yoshino Miya,
Orkin Stuart H.,
Hayashi ShinIchi
Publication year - 2005
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2004-0154
Subject(s) - biology , haematopoiesis , microbiology and biotechnology , embryonic stem cell , macrophage colony stimulating factor , stem cell , stromal cell , stem cell factor , immunology , cancer research , macrophage , biochemistry , in vitro , gene
Transcription factor T‐cell acute lymphocytic leukemia 1 (Tal‐1) is essential for the specification of hematopoietic development. Mice lacking Tal1 fail to generate any hematopoietic precursors. Using our co‐culture system with stromal cells, we demonstrate that enforced expression of the transcription factor PU.1 under tetracycline control in Tal1 ‐null embryonic stem (ES) cells rescues the development of osteoclasts and macrophage–like phagocytes. It was low efficiency compared with wild–type ES cells; other hematopoietic lineage cells of granulocytes, B cells, mast cells, megakaryocytes, and erythroid cells were not generated. Osteoclasts developed in this culture were multinucleated and competent for bone resorption. Their development depended on macrophage colony‐stimulating factor and receptor activator of nuclear factor κB ligand. The majority of cells with the potential to differentiate into osteoclasts expressed fetal liver kinase 1 (Flk‐1) and could be isolated using anti–Flk‐1 antibody. These results suggest that the expression of PU.1 is a critical event for osteoclastogenesis and that Tal‐1 may lie upstream of PU.1 in a regulatory hierarchy during osteoclastogenesis.