Thursday, January 11, 2007
Cambridge scientists have discovered the stage at which some of the cells of a fertilised mammalian egg are fated to develop into stem cells and why this occurs. The findings of the study, which overturn the long-held belief that cells are the same until the fourth cleavage (division) of the embryo, are reported in today's edition of Nature.
After fertilisation, the cells of the embryo at first undergo equal, symmetrical divisions and unequal, asymmetrical ones that direct smaller daughter cells towards the inside of the embryo. These 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.
However, research led by Professor Magdelena Zernicka-Goetz (homepage), University of Cambridge, has revealed evidence to suggest that differences between the embryonic cells are already apparent at the 4-cell-stage.
Continued at "Scientists discover stage at which an embryonic cell is fated to become a stem cell" [Epigenetics]
Based on the Letter to Nature:
Histone arginine methylation regulates pluripotency in the early mouse embryo
It has been generally accepted that the mammalian embryo starts its development with all cells identical, and only when inside and outside cells form do differences between cells first emerge. However, recent findings show that cells in the mouse embryo can differ in their developmental fate and potency as early as the four-cell stage. These differences depend on the orientation and order of the cleavage divisions that generated them. Because epigenetic marks are suggested to be involved in sustaining pluripotency, we considered that such developmental properties might be achieved through epigenetic mechanisms. Here we show that modification of histone H3, through the methylation of specific arginine residues, is correlated with cell fate and potency. Levels of H3 methylation at specific arginine residues are maximal in four-cell blastomeres that will contribute to the inner cell mass (ICM) and polar trophectoderm and undertake full development when combined together in chimaeras. Arginine methylation of H3 is minimal in cells whose progeny contributes more to the mural trophectoderm and that show compromised development when combined in chimaeras. This suggests that higher levels of H3 arginine methylation predispose blastomeres to contribute to the pluripotent cells of the ICM. We confirm this prediction by overexpressing the H3-specific arginine methyltransferase CARM1 in individual blastomeres and show that this directs their progeny to the ICM and results in a dramatic upregulation of Nanog and Sox2. Thus, our results identify specific histone modifications as the earliest known epigenetic marker contributing to development of ICM and show that manipulation of epigenetic information influences cell fate determination.
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