Homeodomain transcription factor Meis1 is a critical regulator of adult bone marrow hematopoiesis.
Hematopoietic stem cells in the bone marrow have the capacity to both self-renew and to generate all cells of the hematopoietic system. The balance of these two activities is controlled by hematopoietic stem cell-intrinsic regulatory mechanisms as well as extrinsic signals from the microenvironment. Here we demonstrate that Meis1, a TALE family homeodomain transcription factor involved in numerous embryonic developmental processes, is selectively expressed in hematopoietic stem/progenitor cells. Conditional Meis1 knockout in adult hematopoietic cells resulted in a significant reduction in the hematopoietic stem/progenitor cells. Suppression of hematopoiesis by Meis1 deletion appears to be caused by impaired self-renewal activity and reduced cellular quiescence of hematopoietic stem/progenitor cells in a cell autonomous manner, resulting in stem cell exhaustion and defective long-term hematopoiesis. Meis1 deficiency down-regulated a subset of Pbx1-dependent hematopoietic stem cell signature genes, suggesting a functional link between them in the maintenance of hematopoietic stem/progenitor cells. These results show the importance of Meis1 in adult hematopoiesis.
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Reina
R
Ariki
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Satoru
S
Morikawa
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yo
Y
Mabuchi
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.
Mayuka
M
Nakatake
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.
Shinya
S
Hidano
Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Hiromitsu
H
Nakauchi
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yumi
Y
Matsuzaki
Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
Takuro
T
Nakamura
Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Ryo
R
Goitsuka
D000367:Age Factors; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D014157:Transcription Factors