A role of jumonji gene in proliferation but not differentiation of megakaryocyte lineage cells

• Published in: Experimental hematology Vol. 29; no. 4; pp. 507 - 514
• Main Authors: Kitajima, Kenji, Kojima, Mizuyo, Kondo, Shunzo, Takeuchi, Takashi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-04-2001
• Subjects: Animals; Cell Count; Cell Differentiation; Cell Division; Colony-Forming Units Assay; DNA-Binding Proteins - analysis; Erythroid-Specific DNA-Binding Factors; Female; GATA1 Transcription Factor; Hematopoietic Stem Cells - cytology; Homozygote; Liver - cytology; Liver - embryology; Male; Megakaryocytes - cytology; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Mutation; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; P-Selectin - analysis; Platelet Factor 4 - analysis; Polycomb Repressive Complex 2; Thrombopoietin - pharmacology; Transcription Factors - analysis; Yolk Sac - cytology; Yolk Sac - embryology
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(00)00686-X

In this study, megakaryocytopoiesis was investigated in the recessive mutant mouse,
jumonji, obtained by a gene-trap strategy.
We investigated the number of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of
jumonji homozygous embryos by in vitro colony forming assay and monitored colony formation from single megakaryocyte progenitors. We also investigated the differentiation of
jumonji-deficient megakaryocytes in terms of the expression of megakaryocyte differentiation markers PF4, CD62P, and GATA-1, proplatelet formation, cytoplasmic maturation, and endomitosis.
We found that the population of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of
jumonji homozygotes increased. A fraction of megakaryocyte progenitors derived from the fetal liver of
jumonji homozygotes formed larger colonies in vitro when compared with controls. This abnormality is caused by delayed growth arrest in the progeny. Immature megakaryocyte progenitors showed this abnormality. The megakaryocytes of
jumonji homozygotes expressed PF4, CD62P, and GATA-1, obtained cytoplasmic maturation, extended proplatelet-like processes, and underwent endomitosis.
The loss of the
jumonji gene causes an increase in the number of megakaryocyte lineage cells. Our data suggest that the
jumonji gene regulates proliferation but not differentiation of megakaryocyte lineage cells.