Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Animals
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Bone Marrow / metabolism*
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Cell Cycle / genetics
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Flow Cytometry
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Gene Expression Profiling
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Hematopoiesis*
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Hematopoietic Stem Cells / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Ecotropic Viral Integration Site 1 Protein
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Oligonucleotide Array Sequence Analysis
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Pre-B-Cell Leukemia Transcription Factor 1
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / metabolism
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Thymus Gland / cytology
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Thymus Gland / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Homeodomain Proteins
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Meis1 protein, mouse
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Myeloid Ecotropic Viral Integration Site 1 Protein
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Neoplasm Proteins
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Pbx1 protein, mouse
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Pre-B-Cell Leukemia Transcription Factor 1
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Transcription Factors
Grants and funding
This work has been supported by Grant-in-Aid for Scientific Research (21658105 and 25111513 to R. G.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.