Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver
Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver
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DOI：
10.1182/blood-2007-01-068528
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发表时间：
2007-08-01
期刊：
影响因子：
20.3
通讯作者：
Wang, Zhu-Gang
中科院分区：
文献类型：
--
作者：
Liu, Xue-Song;Li, Xi-Hua;Wang, Zhu-Gang
Palladin最初被发现在全反式维甲酸诱导的NB 4细胞分化中上调。palladin的破坏导致神经管闭合缺陷、肝疝和胚胎死亡。在这里，我们进一步报告Palict（-/-）胚胎表现出显着的缺陷，红细胞生成的特点是显着减少，在定形红细胞来自胎肝，但不是原始的卵黄囊红细胞。红细胞的减少伴随着成红细胞凋亡的增加和红细胞分化的部分阻断。然而，集落形成试验显示野生型（wt）和突变胎肝或卵黄囊之间在所测试的集落数量和大小方面没有差异。此外，Palld（-/-）胎肝细胞可重建致死辐射小鼠的造血。这些数据强烈表明Palict（-/-）胎肝中红细胞生成不足主要是由于红细胞生成微环境受损。正如预期，Paild（-/-）胎肝中的成红细胞岛被发现紊乱。Palict（-/-）胎肝细胞在体外不能形成成红细胞岛。有趣的是，野生型巨噬细胞可以与野生型或突变型成红细胞形成这样的单位，而突变型巨噬细胞失去了它们结合野生型或突变型成红细胞的能力。这些数据表明，palladin是决定性的红细胞生成和成红细胞岛的形成，特别是，所需的正常功能的巨噬细胞在胎肝中是至关重要的。
Palladin was originally found up-regulated with NB4 cell differentiation induced by alltrans retinoic acid. Disruption of palladin results in neural tube closure defects, liver herniation, and embryonic lethality. Here we further report that Palict(-/-) embryos exhibit a significant defect in erythropoiesis characterized by a dramatic reduction in definitive erythrocytes derived from fetal liver but not primitive erythrocytes from yolk sac. The reduction of erythrocytes is accompanied by increased apoptosis of erythroblasts and partial blockage of erythroid differentiation. However, colony-forming assay shows no differences between wild-type (wt) and mutant fetal liver or yolk sac in the number and size of colonies tested. In addition, Palld(-/-)fetal liver cells can reconstitute hematopoiesis in lethally irradiated mice. These data strongly suggest that deficient erythropoiesis in Palict(-/-) fetal liver is mainly due to a compromised erythropoletic microenvironment. As expected, erythroblastic island in Paild(-/-) fetal liver was found disorganized. Palict(-/-) fetal liver cells fail to form erythroblastic island in vitro. Interestingly, wt macrophages can form such units with either wit or mutant erythroblasts, while mutant macrophages lose their ability to bind wit or mutant erythroblasts. These data demonstrate that palladin is crucial for definitive erythropoiesis and erythroblastic island formation and, especially, required for normal function of macrophages in fetal liver.