Department of Molecular, Cell and Developmental Biology, University of California-Los Angeles, 621 Charles E. Young Drive S., Los Angeles, CA 90095, USA.
Blood. 2010 Oct 28;116(17):3321-30. doi: 10.1182/blood-2010-04-279489. Epub 2010 Jul 13.
Embryonic hematopoiesis starts via the generation of primitive red blood cells (RBCs) that satisfy the embryo's immediate oxygen needs. Although primitive RBCs were thought to retain their nuclei, recent studies have shown that primitive RBCs in mice enucleate in the fetal liver. It has been unknown whether human primitive RBCs enucleate, and what hematopoietic site might support this process. Our data indicate that the terminal maturation and enucleation of human primitive RBCs occurs in first trimester placental villi. Extravascular ζ-globin(+) primitive erythroid cells were found in placental villi between 5-7 weeks of development, at which time the frequency of enucleated RBCs was higher in the villous stroma than in circulation. RBC enucleation was further evidenced by the presence of primitive reticulocytes and pyrenocytes (ejected RBC nuclei) in the placenta. Extravascular RBCs were found to associate with placental macrophages, which contained ingested nuclei. Clonogenic macrophage progenitors of fetal origin were present in the chorionic plate of the placenta before the onset of fetoplacental circulation, after which macrophages had migrated to the villi. These findings indicate that placental macrophages may assist the enucleation process of primitive RBCs in placental villi, implying an unexpectedly broad role for the placenta in embryonic hematopoiesis.
胚胎造血始于产生满足胚胎即时氧气需求的原始红细胞 (RBC)。尽管原始 RBC 被认为保留其核，但最近的研究表明，小鼠的原始 RBC 在胎儿肝脏中去核。目前尚不清楚人类原始 RBC 是否去核，以及造血部位可能支持这一过程。我们的数据表明，人类原始 RBC 的终末成熟和去核发生在妊娠早期胎盘绒毛中。在 5-7 周的发育过程中，胎盘绒毛中发现了血管外 ζ-球蛋白(+)原始红细胞，此时绒毛基质中去核 RBC 的频率高于循环中。胎盘中的原始网织红细胞和丙酮酸细胞（排出的 RBC 核）的存在进一步证明了 RBC 的去核。发现血管外 RBC 与胎盘巨噬细胞相关，后者含有摄入的核。胎儿来源的克隆形成性巨噬细胞祖细胞在胎盘中胎儿胎盘循环开始之前存在于绒毛板中，此后巨噬细胞已迁移到绒毛中。这些发现表明胎盘巨噬细胞可能有助于胎盘绒毛中原始 RBC 的去核过程，这意味着胎盘在胚胎造血中具有出乎意料的广泛作用。
