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Cyclin D3 is essential for megakaryocytopoiesis
Z Wang, Y Zhang, D Kamen, E Lees and K Ravid
Department of Biochemistry, Boston University School of Medicine, MA 02118,
USA.
A normal cell cycle in most eukaryotic cells consists of a tightly
regulated sequence of phases including DNA synthesis (S) followed by a gap
(G2), mitosis (M), and a gap (G1). In the megakaryocytic lineage, the cells
undergo endomitosis, which involves DNA synthesis in the absence of
mitosis, thus giving rise to polyploid cells. We aimed at defining whether
the megakaryocytic cell cycle consists of a continuous S phase or of G1/S
phases and at determining which cyclins are involved in this process.
Studies were performed in primary cultures of mouse bone marrow cells. DNA
synthesis in megakaryocytes was followed by determining incorporation of a
DNA precursor, bromodeoxyuridine (BrdU), into the cells by in situ staining
for BrdU. These experiments showed that no more than 15% of the
recognizable megakaryocytes in normal bone marrow are in the process of
endomitosis, including S phases interrupted by short gaps. Using
immunohistochemistry, we showed that mature megakaryocytes express the G1
phase cyclin and cyclin D3, but not the mitotic cyclin, cyclin B1. Under
culture conditions that selectively promote megakaryocytopoiesis, antisense
oligonucleotides designed to suppress cyclin D3 expression, but not sense
oligonucleotides or antisense oligonucleotides to cyclin B1, dramatically
suppress endomitosis and abrogate megakaryocyte development. Our results
indicate that endoreduplication in megakaryocytes is associated with low
levels of or the absence of cyclin B1, whereas progression through this
process depends on the G1 phase for which cyclin D3 is crucial.
Volume 86,
Issue 10,
pp. 3783-3788,
11/15/1995
Copyright © 1995 by The American Society of Hematology

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