To culture or not to culture?

I think that epigenetics is the coolest. The concept that genes are constantly being modified and therefore turned off or on is amazing. Also the fact that these changes can be passed on to offspring makes it a valid cross-generational model of gene inheritance. I had first heard of epigenetics as the promising new alleyway to study cancer biology. Then came the study of epigenetics in precursor cells as a potential therapeutic. The main problem with this though is that cells act very differently in culture than they do in vivo. Therefore how do researchers keep the cell’s “niche” the same in culture as it is in vivo? Is an identical environment possible? Here’s a study that seeks to explain some of these issues:

Human embryonic stem (hES) cells and fetal mesenchymal stem cells (fMSC ) offer great potential for regenerative therapy strategies. It is therefore important to characterize the properties of these cells in vitro. One major way the environment impacts on cellular physiology is through changes to epigenetic mechanisms. Genes subject to epigenetic regulation via genomic imprinting have been characterized extensively. The integrity of imprinted gene expression therefore provides a measurable index for epigenetic stability. Our results suggest that regardless of stem cell origin, in vitro culture affects the integrity of imprinted gene expression in human cells. We identify biallelic and variably expressed genes that may inform on overall epigenetic stability. As differential methylation did not correlate with imprinted expression changes we propose that other epigenetic effectors are adversely influenced by the in vitro environment. Since DMR integrity was maintained in fMSC but not hES cells, we postulate that specific hES cell derivation and culturing practices result in changes in methylation at DMRs.

Here are a few fun facts about epigenetics from another study that I found:

Epigenetics holds promise to explain some puzzles concerning the risk and course of psychiatric disorders. Epigenetic information is essential as a set of operating instructions for the genome, which is heritable with DNA. The epigenetic regulation of gene expression can plausibly be influenced by the environment of one’s ancestors, prenatal exposures, and by early life events. Some epigenetic mechanisms may alter neurophysiology throughout life by programming gene expression, perhaps in anticipation of certain life experiences. These epigenetic signals are only meta-stable and may be perturbed by stochastic events, errors, or by environmental toxins. This introduction considers the possibility that epigenetic change that may occur as paternal age advances or during fetal adversity may be causally related to the susceptibility for schizophrenia.

So epigenetics may also hold the keys to studying psychiatric disorders as well as cancer and other genetically linked diseases. Though the level of complexity that this adds is overwhelming. If one histone methylation on one histone tail changes the expression of a gene that in turn changes the expression of other genes, then the possibilities are endless. How is it possible that a researcher could track exactly where these modifications are happening and their effects of the rest of the organism?


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