生物谷：來自中國科學(xué)院上海生命科學(xué)研究院/上海第二醫(yī)科大學(xué)健康科學(xué)中心,，上海交通大學(xué)醫(yī)學(xué)院,，瑞金醫(yī)院醫(yī)學(xué)遺傳學(xué)重點(diǎn)實(shí)驗(yàn)
室（State Key Laboratory of Medical Genomics），上海模式生物研究中心（Shanghai Research Center for Model Organisms）的研究人員在之前研究的基礎(chǔ)上進(jìn)一步報(bào)道了palladin缺失（Palld–/–）的小鼠胚胎在死亡之前有嚴(yán)重的貧血表型,，從而提出palladin對(duì)于定向型紅系造血（definitive erythropoiesis）,、骨髓紅系造血島（erythroblastic islands,EI）的形成，尤其是胚胎肝臟巨噬細(xì)胞的正常功能意義重大,。這一研究成果公布在Blood雜志上,。
這一研究由健康科學(xué)研究所王鑄鋼教授領(lǐng)導(dǎo)的遺傳工程實(shí)驗(yàn)室完成，王鑄鋼教授畢業(yè)于新疆醫(yī)學(xué)院醫(yī)學(xué)系,，1995年于美國Memorial Sloan-Kettering Cancer Center 做博士后研究,，1999年從美國回國，被聘為教育部“長(zhǎng)江學(xué)者獎(jiǎng)勵(lì)計(jì)劃”特聘教授,。
回國工作后,，他成功地建立了大規(guī)模、高效的小鼠轉(zhuǎn)基因和基因剔除技術(shù)平臺(tái),，并將之帶入產(chǎn)業(yè)化發(fā)展的軌道,。共研制出80余種轉(zhuǎn)基因和基因剔除小鼠模型，在國際上首次以轉(zhuǎn)基因動(dòng)物證明了AML1-MTG16,、NUP98-PMX1在小鼠造血組織中的特異性表達(dá)可引致轉(zhuǎn)基因小鼠發(fā)生類似人類白血病的表型,；在國際上首次發(fā)現(xiàn)PLAG1基因的高表達(dá)在唾液腺腫瘤發(fā)病中的作用；在國際上首次闡明了Rig-I,、Rig-K和HCCS1等新基因在造血細(xì)胞發(fā)生,、細(xì)胞增殖調(diào)控及胚胎發(fā)育中的重要作用。
近期其實(shí)驗(yàn)室獲得了“中國05-06生命科技年度優(yōu)秀論文評(píng)選”活動(dòng)的二等獎(jiǎng),。
原始出處：
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.
