生物谷:来自中国科学院上海生命科学研究院/上海第二医科大学健康科学中心,上海交通大学医学院,瑞金医院医学遗传学重点实验
室(State Key Laboratory of Medical Genomics),上海模式生物研究中心(Shanghai Research Center for Model Organisms)的研究人员在之前研究的基础上进一步报道了palladin缺失(Palld–/–)的小鼠胚胎在死亡之前有严重的贫血表型,从而提出palladin对于定向型红系造血(definitive erythropoiesis)、骨髓红系造血岛(erythroblastic islands,EI)的形成,尤其是胚胎肝脏巨噬细胞的正常功能意义重大。这一研究成果公布在Blood杂志上。
这一研究由健康科学研究所王铸钢教授领导的遗传工程实验室完成,王铸钢教授毕业于新疆医学院医学系,1995年于美国Memorial Sloan-Kettering Cancer Center 做博士后研究,1999年从美国回国,被聘为教育部“长江学者奖励计划”特聘教授。
回国工作后,他成功地建立了大规模、高效的小鼠转基因和基因剔除技术平台,并将之带入产业化发展的轨道。共研制出80余种转基因和基因剔除小鼠模型,在国际上首次以转基因动物证明了AML1-MTG16、NUP98-PMX1在小鼠造血组织中的特异性表达可引致转基因小鼠发生类似人类白血病的表型;在国际上首次发现PLAG1基因的高表达在唾液腺肿瘤发病中的作用;在国际上首次阐明了Rig-I、Rig-K和HCCS1等新基因在造血细胞发生、细胞增殖调控及胚胎发育中的重要作用。
近期其实验室获得了“中国05-06生命科技年度优秀论文评选”活动的二等奖。
原始出处:
Blood, 1 August 2007, Vol. 110, No. 3, pp. 870-876.
Prepublished online as a Blood First Edition Paper on April 12, 2007; DOI 10.1182/blood-2007-01-068528.
HEMATOPOIESIS
Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver
Xue-Song Liu1,2, Xi-Hua Li1, Yi Wang1, Run-Zhe Shu1,2, Long Wang1,3,4, Shun-Yuan Lu1,3,4, Hui Kong4, Yue-E Jin1, Li-Jun Zhang1, Jian Fei4, Sai-Juan Chen3, Zhu Chen3, Ming-Min Gu1, Zhen-Yu Lu1, and Zhu-Gang Wang1,3,4
1 Laboratory of Genetic Engineering, Department of Medical Genetics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai; 2 Graduate School of Chinese Academy of Sciences, Shanghai; 3 State Key Laboratory of Medical Genomics, Rui-jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; and 4 Shanghai Research Center for Model Organisms, Shanghai, People's Republic of China
Palladin was originally found up-regulated with NB4 cell differentiation induced by all-trans retinoic acid. Disruption of palladin results in neural tube closure defects, liver herniation, and embryonic lethality. Here we further report that Palld–/– 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 Palld–/– fetal liver is mainly due to a compromised erythropoietic microenvironment. As expected, erythroblastic island in Palld–/– fetal liver was found disorganized. Palld–/– fetal liver cells fail to form erythroblastic island in vitro. Interestingly, wt macrophages can form such units with either wt or mutant erythroblasts, while mutant macrophages lose their ability to bind wt 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.