科學(xué)家發(fā)現(xiàn)的一種特定蛋白分子和BMP-4蛋白相互作用，是決定人類干細(xì)胞最終發(fā)育成為胎盤(pán)的關(guān)鍵,。而且這種作用獨(dú)一無(wú)二，無(wú)法復(fù)制或移植,。
據(jù)每日科學(xué)新聞網(wǎng)報(bào)道,，近日科學(xué)家在人類胚胎干細(xì)胞研究領(lǐng)域獲得重大突破，科學(xué)家在人類胚胎干細(xì)胞的發(fā)育過(guò)程中發(fā)現(xiàn)某種特定蛋白分子起到至關(guān)重要的作用,，這種蛋白分子可以使得人類干細(xì)胞最終發(fā)育成為胎盤(pán),，而且這種蛋白分子的特殊作用獨(dú)一無(wú)二，它無(wú)法被其他種類生物所復(fù)制或移植,。
據(jù)報(bào)道,，約翰·霍普金斯大學(xué)的成林召(音譯)博士與他的同事是在一次醫(yī)學(xué)研究中意外發(fā)現(xiàn)這個(gè)重大突破的。當(dāng)時(shí)他們正在對(duì)一種罕見(jiàn)的人類血液紊亂疾病進(jìn)行研究,，尋找引起這種血液疾病的一種名叫PIG-A的基因,。
科研人員將患病基因注射入懷孕母老鼠體內(nèi)以觀察母鼠體內(nèi)小鼠的遺傳特質(zhì)，但在實(shí)驗(yàn)中科學(xué)家發(fā)現(xiàn),，體內(nèi)具有這種血液疾病基因的小老鼠一般在母老鼠體內(nèi)就已死亡,，而沒(méi)有死亡的小老鼠在出生后卻與人類患者的癥狀明顯的不同。
百思不得其解的科學(xué)家們?yōu)檎业皆蛑坏脧南蚶鲜笞⑸涞娜祟惛杉?xì)胞中尋找突破口,?？茖W(xué)家們首先設(shè)法將人干細(xì)胞中的這種突變基因PIG-A基因取出，然而卻始終不能成功,。
后來(lái)轉(zhuǎn)向人類胚胎干細(xì)胞,，希望在胚胎干細(xì)胞未發(fā)育時(shí)就去除掉PIG-A，最終得到所預(yù)想的實(shí)驗(yàn)?zāi)康?。結(jié)果就在這個(gè)實(shí)驗(yàn)中,，科學(xué)家們意外發(fā)現(xiàn)了胚胎干細(xì)胞中存在某種特定的蛋白質(zhì)分子和BMP-4蛋白相互作用，是決定人類干細(xì)胞最終發(fā)育成為胎盤(pán)的關(guān)鍵,。
據(jù)成林召博士介紹,，他們經(jīng)過(guò)一系列復(fù)雜的實(shí)驗(yàn)證明，人類胚胎的分化取決于胚胎干細(xì)胞表層的某種特定蛋白質(zhì)能否接收到BMP-4蛋白所發(fā)出的信號(hào),；而且這種特定蛋白質(zhì)和BMP-4蛋白所產(chǎn)生的作用是獨(dú)一無(wú)二的,，根本無(wú)法在其他生物體內(nèi)復(fù)制或移植，這也就意味著人類的形成是獨(dú)一無(wú)二的,。目前,，科學(xué)家仍然再作進(jìn)一步研究，他們希望以這個(gè)重大突破為開(kāi)始,，揭開(kāi)人類形成的奧秘,，同時(shí)也將有助于進(jìn)一步對(duì)人類胚胎干細(xì)胞進(jìn)行深入的研究。他們這次的重大發(fā)現(xiàn)也將刊登到即將出版的權(quán)威期刊雜志《細(xì)胞干細(xì)胞》(Cell Stem Cell)中。
生物谷推薦原始出處：
Cell Stem Cell, Vol 2, 345-355, 10 April 2008
Trophoblast Differentiation Defect in Human Embryonic Stem Cells Lacking PIG-A and GPI-Anchored Cell-Surface Proteins
Guibin Chen,1,2 Zhaohui Ye,1,2,4 Xiaobing Yu,1,2 Jizhong Zou,1,2 Prashant Mali,1,2,5 Robert A. Brodsky,3 and Linzhao Cheng1,2,3,4,
1 Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
4 Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5 Graduate Program in Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Summary
Pluripotent human embryonic stem (hES) cells can differentiate into various cell types derived from the three embryonic germ layers and extraembryonic tissues such as trophoblasts. The mechanisms governing lineage choices of hES cells are largely unknown. Here, we report that we established two independent hES cell clones lacking a group of cell surface molecules, glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs). The GPI-AP deficiency in these two hES clones is due to the deficiency in the gene expression of PIG-A (phosphatidyl-inositol-glycan class A), which is required for the first step of GPI synthesis. GPI-AP-deficient hES cells were capable of forming embryoid bodies and initiating cell differentiation into the three embryonic germ layers. However, GPI-AP-deficient hES cells failed to form trophoblasts after differentiation induction by embryoid body formation or by adding exogenous BMP4. The defect in trophoblast formation was due to the lack of GPI-anchored BMP coreceptors, resulting in the impairment of full BMP4 signaling activation in the GPI-AP-deficient hES cells. These data reveal that GPI-AP-enhanced full activation of BMP signaling is required for human trophoblast formation.
