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TISSUE-SPECIFIC STEM CELLS

CD41⁺/CD45⁺ Cells Without Acetylcholinesterase Activity Are Immature and a Major Megakaryocytic Population in Murine Bone Marrow

^aMolecular Medical Science Institute,
^bTheranostics Research Center, and
^cBioinformatics, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan;
^dDepartment of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan

Key Words. Bone marrow • Thrombopoiesis • Mouse • Microarray • Megakaryocytes

Correspondence: Shinji Sogo, Ph.D., Molecular Medical Science Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima, Japan. Telephone: 81-88-665-2126; Fax: 81-88-665-5662; e-mail: s_sogo{at}research.otsuka.co.jp

Received June 13, 2006; accepted for publication December 12, 2006.
First published online in STEM CELLS EXPRESS   January 18, 2007.



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 semiquantitative polymerase chain reaction 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 ß1-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 antitumor agent, mitomycin-C, Lin^–/CD41⁺/CD45⁺/AChE^– MKs led to an increase in AChE⁺ MKs and subsequent PLT recovery with interleukin-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.

Disclosure of potential conflicts of interest is found at the end of this article.