Embryonic megakaryopoiesis starts in the yolk sac on gestational day 7.5 as part of the primitive wave of hematopoiesis, and it continues in the fetal liver when this organ is colonized by hematopoietic progenitors between day 9.5 and 10.5, as the definitive hematopoiesis wave. We characterized the precise phenotype of embryo megakaryocytes in the liver at gestational day 11.5, identifying them as CD41⁺⁺CD45-CD9⁺⁺CD61⁺MPL⁺CD42c⁺ tetraploid cells that express megakaryocyte-specific transcripts and display differential traits when compared to those present in the yolk sac at the same age. In contrast to megakaryocytes from adult bone marrow, embryo megakaryocytes are CD45^- until day 13.5 of gestation, as are both the megakaryocyte progenitors and megakaryocyte/erythroid-committed progenitors. At gestational day 11.5, liver and yolk sac also contain CD41⁺CD45⁺ and CD41⁺CD45^- cells. These populations, and that of CD41⁺⁺CD45^-CD42c⁺ cells, isolated from liver, differentiate in culture into CD41⁺⁺CD45^-CD42c⁺ proplatelet-bearing megakaryocytes. Also present at this time are CD41^-CD45⁺⁺CD11b⁺ cells, which produce low numbers of CD41⁺⁺CD45^-CD42c⁺ megakaryocytes in vitro, as do fetal liver cells expressing the macrophage-specific Csf receptor-1 (Csf1r/CD115) from MaFIA transgenic mice, which give rise poorly to CD41⁺⁺CD45^-CD42c⁺ embryo megakaryocytes both in vivo and in vitro In contrast, around 30% of adult megakaryocytes (CD41⁺⁺CD45⁺⁺CD9⁺⁺CD42c⁺) from C57BL/6 and MaFIA mice express CD115. We propose that differential pathways operating in the mouse embryo liver at gestational day 11.5 beget CD41⁺⁺CD45^-CD42c⁺ embryo megakaryocytes that can be produced from CD41⁺CD45^- or from CD41⁺CD45⁺ cells, at difference from those from bone marrow.

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