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, University of Cambridge, has revealed evidence to suggest 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. And those differences depend on the orientation and order of the very first cleavage divisions of the embryo.

Professor Zernicka-Goetz said, "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."

The study also found cell fate and transcription activity is determined by the level of a methylated form of histone H3, one of the basic proteins around which DNA is packaged and which when modified in this way affects gene expression. They found that the higher the levels of this modified form of histone H3, the more predisposed the mammalian embryonic cells were to develop the qualities of inner embryonic cells, a population that have stem-cell-like properties. Thus, their results show that manipulating epigenetic information in this protein in early mouse embryos can influence cell fate determination.

cam.ac

"The exciting findings in our work indicate that there is a microRNA gene-expression pattern that is unique to pancreatic tumors, and this might be useful in diagnosing pancreatic cancer in the future."

For this study, the researchers used a technique developed by Schmittgen and a group of colleagues in 2004 to measure miRNA in small tissue samples. The method is based on a technology called real-time PCR profiling, which is highly sensitive and requires very small amounts of tissue, Schmittgen says.

The researchers used the method to compare the levels of 225 miRNAs in samples of pancreatic tumors from patients with adjacent normal tissue, normal pancreatic tissue and nine pancreatic cancer cell lines.

Computer analysis of the data identified a pattern of miRNAs that were present at increased or decreased levels in pancreatic tumor tissue compared with normal tissue. The analysis correctly identified 28 out of 28 pancreatic tumors, 11 of 15 adjacent benign tissues and six of six normal tissues.

Levels of some miRNAs were increased by more than 30- and 50-fold, with a few showing decreased levels of eight- to 15-fold.

Schmittgen and his colleagues are now working to learn which of the miRNAs they identified are most important for pancreatic cancer development, and if some are found only in pancreatic cancer and not in other types of cancer.

osuccc.osu/