Regulation of the embryonic erythropoietic niche: a future perspective.
Regulation of the embryonic erythropoietic niche: a future perspective.
复制标题
DOI：
10.5045/br.2017.52.1.10
复制
发表时间：
2017-03
期刊：
影响因子：
2.2
通讯作者：
Sugiyama D
中科院分区：
文献类型：
--
作者：
Yumine A;Fraser ST;Sugiyama D
红细胞的产生，称为红细胞生成，在发育中的小鼠胚胎中以两波发生：首先是原始红细胞生成，然后是定形红细胞生成。在小鼠胚胎中，原始和定形红细胞生成都起源于胚外卵黄囊。当这些器官形成时，确定波然后迁移到胎儿肝脏、胎儿脾脏和胎儿骨髓。胎肝是妊娠中期后造血细胞扩增和红系成熟的主要器官。表达关键细胞因子如干细胞因子（SCF）、血小板生成素（TPO）和胰岛素样生长因子IGF 1和IGF 2的红细胞生成小生境支持胎儿肝脏中的造血扩增。以前，我们的小组证明DLK 1+肝母细胞通过促红细胞生成素和SCF释放以及细胞外基质沉积支持胎肝造血。Map 2k 4 −/−小鼠胚胎中DLK 1+肝母细胞的缺失导致胎肝中造血细胞数量减少。发现编码蛋白酶和肽酶的基因在DLK 1+成肝细胞中高度表达。利用这一知识，并假设这些蛋白酶和肽酶正在产生小的、具有潜在生物活性的肽，我们评估了一系列肽在体外支持红细胞生成的能力。我们鉴定KS-13（PCT/JP 2010/067011）为促红细胞生成肽-一种增强由祖细胞产生红细胞的肽。在这里，我们讨论了调节胚胎红细胞生成的元素，特别注意小生境细胞，并展示了如何将这些知识应用于识别具有潜在治疗能力的小生境衍生肽。
The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation. The erythropoietic niche, which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin (TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic expansion in the fetal liver. Previously, our group demonstrated that DLK1+ hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF release as well as extracellular matrix deposition. Loss of DLK1+ hepatoblasts in Map2k4−/− mouse embryos resulted in decreased numbers of hematopoietic cells in fetal liver. Genes encoding proteinases and peptidases were found to be highly expressed in DLK1+ hepatoblasts. Capitalizing on this knowledge, and working on the assumption that these proteinases and peptidases are generating small, potentially biologically active peptides, we assessed a range of peptides for their ability to support erythropoiesis in vitro. We identified KS-13 (PCT/JP2010/067011) as an erythropoietic peptide-a peptide which enhances the production of red blood cells from progenitor cells. Here, we discuss the elements regulating embryonic erythropoiesis with special attention to niche cells, and demonstrate how this knowledge can be applied in the identification of niche-derived peptides with potential therapeutic capability.