Friday, May 9, 2008

Cell Pluripotency and RNA interference

I recently blogged a small post about the rush to stem cells. In 2006, it was proven that by introducing 4 transcription factors in fibroblasts cells, these would reprogram themselves into pluripotent cells. Science magazine has a "perspective" piece on the current state of research.

Pluripotency is a cell state that can give rise to any type of cell. Knowing that the body has 200 cell types, rebuilding pluripotent cells is a goal in and on itself. The cells are called "induced pluripotent stem cells" or iPS cells. From a ethics and religious standpoint, the advantage of these cells is that they do not derive from Embryonic Stem cells (ES cells) and therefore do not run into the same objections.

From Science:

What this drawing shows is that the cells that are obtained, the iPS cells are very similar from ES cells. Whereas the path on the right use embryos (hence the moral objections) the left path uses fibroblasts or Gastric cells (stuff from your gut) . It is unknown as of yet whether other types of cells such as neurons can be reprogrammed to be iPS cells. It is also not completely understood how the reprogrammable cells are reprogrammed.

However that much is known: the ES cells are 'specialized' by way of miRNA. Micro RNA are snippets of RNA code usually fairly small in size, say 30-50 bases, whose main property is that they bind to a DNA site and INTERFERE with the production of proteins. It is a SILENCING mechanisms. The field of miRNA interference, or RNAi, is popular. It seems that an ES cell becomes a specialized cell by a given cocktail of miRNA and a resulting multi-RNAi expression. In other words, ALL CELLS are iPS in their genetic code (they all have the same genetic code) but by applying different filters of RNAi, the cells specializes. In other words, cell specialization and reprogramming seems to be an epi-genetic phenomena. The article speculates that the transcription factors that have been proven to induce PS state in cells basically interfere with the interference or over promotes the protein expression associated with PS state.

The article concludes that the main advantage of iPS cell technology is that it is patient specific. In other words most of the problems of organ transplant and the rejection mechanism associated with the immune system detecting an alien body could be circumvented. Proving that these cells are stable is important. Today the delivery of protein cocktail to the cell uses viral packaging as viruses are good at attaching to cells and delivering DNA cargo to a cell. Developping non-viral delivery is important you wouldn't want your whole body resetting in "iPS" state under treatment. The study of reprogramming up and down the iPS<->Special cell tree is important. The study of the STATE MACHINE OF CELLS is under way.

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