Submitted on June 13, 2006
Accepted on December 12, 2006
Tissue-Specific Stem Cells
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CD41+/CD45+ cells without acetylcholinesterase activity are immature and a major megakaryocytic population in murine bone marrow
Kuniko Matsumura-Takeda 1,
Shinji Sogo 2*,
Yoshimasa Isakari 1,
Yasuo Harada 2,
Kinue Nishioka 2,
Takuma Kawakami 3,
Toshihide Ono 4,
Takao Taki 2
1 Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan; Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan
2 Molecular Medical Science Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
3 Theranostics Research Center, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
4 Bioinformatics, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
* To whom correspondence should be addressed. E-mail: s_sogo{at}research.otsuka.co.jp.
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Abstract |
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Murine megakaryocytes (MKs) are defined by CD41/CD61-expression and acetylcholinesterase (AChE) activity; however, their stages of differentiation in bone marrow (BM) have not been fully elucidated. In murine lineage-negative (Lin-)/CD45+ BM cells, we found CD41+ MKs without AChE activity (AChE-) except for CD41++ MKs with AChE activity (AChE+), in which CD61 expression was similar to their CD41 level. Lin-/CD41+/CD45+/AChE- MKs could differentiate into AChE+, with an accompanying increase in CD41/CD61 during in vitro culture. Both proplatelet formation (PPF) and platelet (PLT) production for Lin-/CD41+/CD45+/AChE- MKs were observed later than for Lin-/CD41++/CD45+/AChE+ MKs; whereas, MK-progenitors were scarcely detected in both subpopulations. GeneChip and semi-quantitative PCR analyses revealed that the Lin-/CD41+/CD45+/AChE- MKs are assigned at the stage between the progenitor and PPF preparation phases in respect to the many MK/PLT-specific gene-expressions including beta1-tubulin. In normal mice, the number of Lin-/CD41+/CD45+/AChE- MKs was 100 times higher than that of AChE+ MKs in BM. When MK-destruction and consequent thrombocytopenia were caused by an anti-tumor agent, mitomycin-C, Lin-/CD41+/CD45+/AChE- MKs led to an increase in AChE+ MKs and subsequent PLT recovery with IL-11-administration. It was concluded that MKs in murine BM at least in part consist of immature Lin-/CD41+/CD45+/AChE- MKs and more differentiated Lin-/CD41++/CD45+/AChE+ MKs. Immature Lin-/CD41+/CD45+/AChE- MKs are a major MK-population compared with AChE+ MKs in BM and play an important role in rapid PLT recovery in vivo.
