OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets

Yumiko Matsubara, Yukako Ono, Hidenori Suzuki, Fumio Arai, Toshio Suda, Mitsuru Murata, Yasuo Ikeda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Platelets are essential for hemostatic plug formation and thrombosis. The mechanisms of megakaryocyte (MK) differentiation and subsequent platelet production from stem cells remain only partially understood. The manufacture of megakaryocytes (MKs) and platelets from cell sources including hematopoietic stem cells and pluripotent stem cells have been highlighted for studying the platelet production mechanisms as well as for the development of new strategies for platelet transfusion. The mouse bone marrow stroma cell line OP9 has been widely used as feeder cells for the differentiation of stem cells into MK lineages. OP9 cells are reported to be pre-adipocytes. We previously reported that 3T3-L1 pre-adipocytes differentiated into MKs and platelets. In the present study, we examined whether OP9 cells differentiate into MKs and platelets using MK lineage induction (MKLI) medium previously established to generate MKs and platelets from hematopoietic stem cells, embryonic stem cells, and pre-adipocytes. OP9 cells cultured in MKLI medium had megakaryocytic features, i.e., positivity for surface markers CD41 and CD42b, polyploidy, and distinct morphology. The OP9-derived platelets had functional characteristics, providing the first evidence for the differentiation of OP9 cells into MKs and platelets. We then analyzed gene expressions of critical factors that regulate megakaryopoiesis and thrombopoiesis. The gene expressions of p45NF-E2, FOG, Fli1, GATA2, RUNX1, thrombopoietin, and c-mpl were observed during the MK differentiation. Among the observed transcription factors of MK lineages, p45NF-E2 expression was increased during differentiation. We further studied MK and platelet generation using p45NF-E2-overexpressing OP9 cells. OP9 cells transfected with p45NF-E2 had enhanced production of MKs and platelets. Our findings revealed that OP9 cells differentiated into MKs and platelets in vitro. OP9 cells have critical factors for megakaryopoiesis and thrombopoiesis, which might be involved in a mechanism of this differentiation. p45NF-E2 might also play important roles in the differentiation of OP9 cells into MK lineages cells.

Original languageEnglish
Article numbere58123
JournalPLoS One
Volume8
Issue number3
DOIs
Publication statusPublished - 2013 Mar 1

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megakaryocytes
Megakaryocytes
Platelets
Bone Marrow Cells
bone marrow
Bone
Blood Platelets
Stem cells
cells
adipocytes
Adipocytes
cell differentiation
Thrombopoiesis
stem cells
Cell Differentiation
Gene expression
Hematopoietic Stem Cells
Stem Cells
Feeder Cells
Thrombopoietin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Matsubara, Y., Ono, Y., Suzuki, H., Arai, F., Suda, T., Murata, M., & Ikeda, Y. (2013). OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets. PLoS One, 8(3), [e58123]. https://doi.org/10.1371/journal.pone.0058123

OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets. / Matsubara, Yumiko; Ono, Yukako; Suzuki, Hidenori; Arai, Fumio; Suda, Toshio; Murata, Mitsuru; Ikeda, Yasuo.

In: PLoS One, Vol. 8, No. 3, e58123, 01.03.2013.

Research output: Contribution to journalArticle

Matsubara, Y, Ono, Y, Suzuki, H, Arai, F, Suda, T, Murata, M & Ikeda, Y 2013, 'OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets', PLoS One, vol. 8, no. 3, e58123. https://doi.org/10.1371/journal.pone.0058123
Matsubara, Yumiko ; Ono, Yukako ; Suzuki, Hidenori ; Arai, Fumio ; Suda, Toshio ; Murata, Mitsuru ; Ikeda, Yasuo. / OP9 Bone Marrow Stroma Cells Differentiate into Megakaryocytes and Platelets. In: PLoS One. 2013 ; Vol. 8, No. 3.
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