School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
Laboratory of Membrane Biology, New York Blood Center, New York, NY 10065, USA.
Cells. 2024 Jul 5;13(13):1149. doi: 10.3390/cells13131149.
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 , and downstream target 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.
红细胞生成首先在卵黄囊中作为过渡的“原始”形式发生，然后在胎儿发育过程中逐渐被胎儿肝脏 (FL) 中的“定型”形式取代，在出生后被骨髓 (BM) 取代。虽然众所周知原始红细胞生成和定型红细胞生成之间存在差异，但 FL 和 BM 定型红细胞生成之间的相似性和差异尚未得到研究。在这里，我们对从 E16.5 FL 和成人 BM 分选的所有成熟阶段的红系祖细胞和前体细胞进行了全面比较。我们发现，所有成熟阶段的 FL 细胞都比其 BM 对应物大。我们进一步发现，FL BFU-E 细胞的分裂速度更快，经历了更多的细胞分裂。转录组比较显示，FL BFU-E 中表达增加的基因在细胞分裂中富集。有趣的是，FL BFU-E 中糖皮质激素受体 、 和下游靶基因的表达水平明显更高，表明 Nr3c1-Myc-Ccna2 轴在增强 FL BFU-E 细胞的增殖/细胞分裂中的作用。在 CFU-E 阶段，FL CFU-E 中与血红蛋白生物合成相关的基因表达水平要高得多，表明产生了更多的血红蛋白。在终末红细胞生成过程中，FL 和 BM 之间的基因表达总体时间模式保持一致。虽然与翻译、三羧酸循环和缺氧反应相关的生物学过程在 FL 成红细胞中上调，与抗病毒信号通路相关的生物学过程在 BM 成红细胞中上调。我们的发现揭示了 FL 和 BM 定型红细胞生成之间以前未被认识到的差异，并为红细胞生成提供了新的见解。
