科学家发现的一种特定蛋白分子和BMP-4蛋白相互作用,是决定人类干细胞最终发育成为胎盘的关键。而且这种作用独一无二,无法复制或移植。
据每日科学新闻网报道,近日科学家在人类胚胎干细胞研究领域获得重大突破,科学家在人类胚胎干细胞的发育过程中发现某种特定蛋白分子起到至关重要的作用,这种蛋白分子可以使得人类干细胞最终发育成为胎盘,而且这种蛋白分子的特殊作用独一无二,它无法被其他种类生物所复制或移植。
据报道,约翰·霍普金斯大学的成林召(音译)博士与他的同事是在一次医学研究中意外发现这个重大突破的。当时他们正在对一种罕见的人类血液紊乱疾病进行研究,寻找引起这种血液疾病的一种名叫PIG-A的基因。
科研人员将患病基因注射入怀孕母老鼠体内以观察母鼠体内小鼠的遗传特质,但在实验中科学家发现,体内具有这种血液疾病基因的小老鼠一般在母老鼠体内就已死亡,而没有死亡的小老鼠在出生后却与人类患者的症状明显的不同。
百思不得其解的科学家们为找到原因只得从向老鼠注射的人类干细胞中寻找突破口。科学家们首先设法将人干细胞中的这种突变基因PIG-A基因取出,然而却始终不能成功。
后来转向人类胚胎干细胞,希望在胚胎干细胞未发育时就去除掉PIG-A,最终得到所预想的实验目的。结果就在这个实验中,科学家们意外发现了胚胎干细胞中存在某种特定的蛋白质分子和BMP-4蛋白相互作用,是决定人类干细胞最终发育成为胎盘的关键。
据成林召博士介绍,他们经过一系列复杂的实验证明,人类胚胎的分化取决于胚胎干细胞表层的某种特定蛋白质能否接收到BMP-4蛋白所发出的信号;而且这种特定蛋白质和BMP-4蛋白所产生的作用是独一无二的,根本无法在其他生物体内复制或移植,这也就意味着人类的形成是独一无二的。目前,科学家仍然再作进一步研究,他们希望以这个重大突破为开始,揭开人类形成的奥秘,同时也将有助于进一步对人类胚胎干细胞进行深入的研究。他们这次的重大发现也将刊登到即将出版的权威期刊杂志《细胞干细胞》(Cell Stem Cell)中。
生物谷推荐原始出处:
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.