PDF(Pubmed)
Abstract：
Erythropoiesis occurs first in the yolk sac as a transit \"primitive\" form, then is gradually replaced by the \"definitive\" form in the fetal liver (FL) during fetal development and in the bone marrow (BM) postnatally. While it is well known that differences exist between primitive and definitive erythropoiesis, the similarities and differences between FL and BM definitive erythropoiesis have not been studied. Here we performed comprehensive comparisons of erythroid progenitors and precursors at all maturational stages sorted from E16.5 FL and adult BM. We found that FL cells at all maturational stages were larger than their BM counterparts. We further found that FL BFU-E cells divided at a faster rate and underwent more cell divisions than BM BFU-E. Transcriptome comparison revealed that genes with increased expression in FL BFU-Es were enriched in cell division. Interestingly, the expression levels of glucocorticoid receptor Nr3c1, Myc and Myc downstream target Ccna2 were significantly higher in FL BFU-Es, indicating the role of the Nr3c1-Myc-Ccna2 axis in the enhanced proliferation/cell division of FL BFU-E cells. At the CFU-E stage, the expression of genes associated with hemoglobin biosynthesis were much higher in FL CFU-Es, indicating more hemoglobin production. During terminal erythropoiesis, overall temporal patterns in gene expression were conserved between the FL and BM. While biological processes related to translation, the tricarboxylic acid cycle and hypoxia response were upregulated in FL erythroblasts, those related to antiviral signal pathway were upregulated in BM erythroblasts. Our findings uncovered previously unrecognized differences between FL and BM definitive erythropoiesis and provide novel insights into erythropoiesis.
摘要：
红细胞生成首先以过渡“原始”形式出现在卵黄囊中，然后在胎儿发育期间在胎儿肝脏（FL）和出生后在骨髓（BM）中逐渐被“确定”形式取代。虽然众所周知，原始红细胞生成和确定性红细胞生成之间存在差异，尚未研究FL和BM确定性红细胞生成之间的异同。在这里，我们对E16.5FL和成年BM中所有成熟阶段的红系祖细胞和前体进行了全面比较。我们发现在所有成熟阶段的FL细胞都大于其BM对应物。我们进一步发现，FLBFU-E细胞比BMBFU-E以更快的速度分裂并经历更多的细胞分裂。转录组比较显示，在FLBFU-Es中表达增加的基因在细胞分裂中富集。有趣的是,糖皮质激素受体Nr3c1、Myc和Myc下游靶标Ccna2的表达水平在FLBFU-Es中显著升高,表明Nr3c1-Myc-Ccna2轴在FLBFU-E细胞增强的增殖/细胞分裂中的作用。在CFU-E阶段,与血红蛋白生物合成相关的基因在FLCFU-Es中表达高得多，表明更多的血红蛋白生产。在终末期红细胞生成期间，基因表达的总体时间模式在FL和BM之间是保守的。虽然与翻译有关的生物过程，三羧酸循环和缺氧反应在FL成红细胞中上调，与抗病毒信号通路相关的信号在BM成红细胞中上调。我们的发现揭示了FL和BM确定性红细胞生成之间以前未认识到的差异，并为红细胞生成提供了新的见解。
