Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.
Prep1, a TALE-family homeodomain transcription factor, has been demonstrated to play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis. In the present study, we generated hematopoietic- and endothelial cell-specific Prep1-deficient mice and demonstrated that expression of Prep1 in the hematopoietic cell compartment is not essential for either embryonic or adult hematopoiesis, although its absence causes significant hematopoietic abnormalities in the adult bone marrow. Loss of Prep1 promotes cell cycling of hematopoietic stem/progenitor cells (HSPC), leading to the expansion of the HSPC pool. Prep1 deficiency also results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation. Maturation of T cells and B cells is also perturbed in Prep-deficient mice. These findings provide novel insight into the pleiotropic roles of Prep1 in adult hematopoiesis that were unrecognized in previous studies using germline Prep1 hypomorphic mice.
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Kentaro
K
Yoshioka
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Akihisa
A
Oda
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Chihiro
C
Notsu
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Takafumi
T
Ohtsuka
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Yasuhiro
Y
Kawai
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Sadafumi
S
Suzuki
Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
Takuro
T
Nakamura
Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Yo
Y
Mabuchi
Department of Cancer Biology, Faculty of Medicine, Shimane University, Izumo-shi, Shimane, Japan.
Yumi
Y
Matsuzaki
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Ryo
R
Goitsuka
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*
D018398:Homeodomain Proteins; C491412:Pknox1 protein, mouse; D012333:RNA, Messenger