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Nature:胚胎细胞分化时间提前到只有四个细胞的发育阶段

来源:华文生技网 2007-01-17 09:18

剑桥大学研究人员发现,从只有四个细胞的早期阶段开始,小鼠的细胞命运就有所不同了。剑桥大学的Magdelena Zernicka-Goetz教授及其研究小组,发现细胞间的差异其实早在四细胞期时就形成了,此时胚胎细胞间就已经存在差异。

之前,科学界推测胚胎的早期发育可能存在着一种表观遗传修饰,这是一种非DNA编码的机制,而这篇研究证明事实的确如此。

研究人员发现,细胞命运和转录活性是由甲基化组蛋白H3的水平决定的。DNA在细胞核中围绕在H3以及其它一些组蛋白周围,如果组蛋白H3发生甲基化,会直接影响基因的表现。

研究人员发现这种组蛋白H3甲基化修饰的程度越高,胚胎细胞就越容易向内细胞团中干细胞方向发展。因此,他们的研究显示,在早期小鼠胚胎中,组蛋白H3的表观遗传修饰,会直接影响细胞们的命运。研究结果刊载于1月11日的Nature中。

英文原文:

Scientists discover stage when embryonic cells become stem cells 

Scientists at the University of Cambridge have discovered the stage at which some of the cells of fertilized mammalian eggs are fated to become stem cells.

These findings are contrary to the long-held belief that cells are the same until the fourth cleavage of the embryo.

The study, published in Nature magazine, also lists the causes behind this phenomenon.

The researchers say that after fertilization, the embryonic cells at first undergo equal, symmetrical divisions and unequal, asymmetrical ones that direct smaller daughter cells towards the inside of the embryo, and then they become the inner cell mass of stem cells.

Previously, it was believed that the mammalian embryo starts its development with identical cells, and only as these inside and outside cells form do differences between cells first emerge.

But Professor Magdelena Zernicka-Goetz claims to having found evidence suggesting that differences between the embryonic cells are already apparent at the 4-cell-stage, before the cells become partitioned between the inside or outside of the embryo.

The lead researcher said that those differences depend on the orientation and order of the very first cleavage divisions of the embryo.

"Our findings were surprising since they showed that cells of the mammalian embryo first start to differ from each other much earlier in development than previously supposed but also they give us a real clue on how to manipulate embryonic cells so that they will develop with the properties of the natural stem cells of the embryo," said Professor Zernicka-Goetz.

The study also found that the level of a methylated form of histone H3, one of the basic proteins around which DNA is packaged and affects the gene expression when modified, determined the cell fate and transcription activity.

They found that the higher the levels of modified form of histone, the more predisposed the mammalian embryonic cells were to develop the qualities of inner embryonic cells, a population that have stem-cell-like properties.

Their findings show that manipulating epigenetic information in this protein in early mouse embryos can influence cell fate determination.
 

 

 

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