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Blood, 1 April 2001, Vol. 97, No. 7, pp. 2016-2022
HEMATOPOIESIS
Evidence for the presence of murine primitive
megakarycytopoiesis in the early yolk sac
Ming-jiang Xu,
Sahoko Matsuoka,
Feng-Chun Yang,
Yasuhiro Ebihara,
Atsushi Manabe,
Ryuhei Tanaka,
Mitsuoki Eguchi,
Shigetaka Asano,
Tatsutoshi Nakahata, and
Kohichiro Tsuji
From the Department of Clinical Oncology and Molecular
Medicine, The Institute of Medical Science, The University of Tokyo,
Tokyo, Japan; Second Department of Pediatrics, Dokkyo University School
of Medicine, Tochigi, Japan; and Department of Pediatrics, Kyoto
University, Kyoto, Japan.
During mouse embryogenesis, primitive erythropoiesis occurs
in blood islands of the yolk sac (YS) on the seventh day of gestation. This study demonstrated for the first time the presence of unique primitive megakaryocytic (Mk) progenitors in the early YS, which disappeared by 13.5 days postcoitum (dpc). When 7.5 dpc YS cells were
incubated in the presence of stem cell factor (SCF), interleukin (IL)-3, IL-6, erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony-stimulating factor in methylcellulose clonal culture, not only erythroid bursts but also megakaryocyte colonies were
observed. The megakaryocytes in the colonies matured to proplatelet stages and produced platelets as early as day 3 of culture, much earlier than those from adult bone marrow, although their ploidy class
was lower. These megakaryocytes were stained with acetylcholine esterase, and expressed platelet glycoprotein (GP)Ib , GPIIIa, and
platelet factor 4 by reverse transcription-polymerase chain reaction
analysis. The analysis of hemoglobin types in erythrocytes obtained
from hematopoietic multilineage colonies containing the megakaryocytes
indicated that the Mk progenitors originated from primitive
hematopoiesis. The primitive Mk progenitors formed colonies in the
absence of any cytokines in fetal bovine serum (FBS)-containing culture, and SCF, IL-3, EPO, and TPO significantly enhanced the Mk
colony formation. In FBS-free culture, however, no colony formation was
induced without these cytokines. Because megakaryocytes were detected
in 8.5-dpc YS, these unique primitive Mk progenitors may rapidly mature
and give rise to platelets to prevent hemorrhage in the simultaneously
developing blood vessels until definitive hematopoiesis begins to
produce platelets.
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