AML1/Runx1 negatively regulates quiescent hematopoietic stem cells in adult hematopoiesis.
Transcription factor AML1/Runx1, initially isolated from the t(8;21) chromosomal translocation in human leukemia, is essential for the development of multilineage hematopoiesis in mouse embryos. AML1 negatively regulates the number of immature hematopoietic cells in adult hematopoiesis, whereas it is required for megakaryocytic maturation and lymphocytic development. However, it remains yet to be determined how AML1 contributes to homeostasis of hematopoietic stem cells (HSCs). To address this issue, we analyzed in detail HSC function in the absence of AML1. Notably, cells in the Hoechst 33342 side population fraction are increased in number in AML1-deficient bone marrow, which suggests enrichment of quiescent HSCs. We also found an increase in HSC number within the AML1-deficient bone marrow using limiting dilution bone marrow transplantation assays. These results indicate that the number of quiescent HSCs is negatively regulated by AML1.
Ichikawa
Motoshi
M
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Goyama
Susumu
S
Asai
Takashi
T
Kawazu
Masahito
M
Nakagawa
Masahiro
M
Takeshita
Masataka
M
Chiba
Shigeru
S
Ogawa
Seishi
S
Kurokawa
Mineo
M
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D003114:Colony-Forming Units Assay; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse