Skinner - epigenetics from conception

So a sperm and an egg come together and form what’s called a zygote. So that’s the first cell okay and it’s the first cell of the developing embryo that’s going to go forward. So the DNA from the sperm gets together with the DNA from the – which is half the DNA comes from here and half the DNA came from the eggs – they come together and they form and fuse and they form this what’s called a diploid but it has all their DNA for one cell present. And then this zygote then starts to have certain activities going on that will lead it to divide. It’s called a cleavage event and it basically divides into two cells.

At that point you now have an early developing embryo. And there will be more and more cell divisions going forward and eventually you have an embryo that doesn’t have any defined structure per se and it’s right before it starts to develop a structure and sort of starts developing a fetus eventually and so forth. So there’s a cell type in the early embryo called an embryonic stem cell. Stem cells that are within that early embryo. And these are what are called – these cells have the capacity to turn into any cell in the body. And so as the embryo develops then essentially this cell will turn into a neuron and the brain will sort of develop from it, this one will turn into a liver and a hepatocyte develops from it. All these different cells come from this population of stem cells.

So one of the questions that nobody really ever asked before was “Well what forms the stem cells?” It turns out that the sperm and the egg have a certain level of epigenetics. DNA methylation is one, there’s other sort of things going on. There’s epigenetics in the sperm and epigenetics in the egg, in terms of the methylation of DNA which has a chemical mark on the DNA that actually will help turn genes on and off and so forth. So these come together and there’s full-blown DNA methylation of this zygote. The first cleavage event then, what happens is, immediately the DNA methylation, all these chemical modifications of DNA, they start to get erased. So it’s that over, in the first four or five cell divisions all of a sudden the DNA methylation is erased and you have a much, much lower, it’s not completely zero, but it’s in the 10% – 15% range.

So essentially then, this cell that is a stem cell is now pluripotent or totipotent. It can turn into anything because there’s no DNA methylation. And when you actually start remethylating to make a neuron there’s a cascade of methylation events to eventually get a neuron. Or for a heart cell it’s a cascade of events to get a cardiac heart cell. All these cells will come from this population and it’s the methylation that actually determines the lineage of that cell and what it’s going turn into. So right at the level of conception you have this DNA methylation ratio and then it goes back up in a cell-specific manner. So epigenetics is critical from the very beginning.

And then what happens during early development when it’s just in that developing process, if you get an environmental stressor: a chemical, nutrition, stress, a whole series of environmental stressors that affect this early developmental sort of fetus or something or even postnatally – then essentially, you alter that programming. So you get a neuron that becomes a neuron but now it has a different epigenetics and may not function as it would’ve normally. Or a cardiac cell that basically was going become a heart now it basically you’re going get potentially a susceptibility to get heart disease because of those early insults when that programming is occurring. So epigenetics is required throughout all of development just like the gene expression in the genetics is as well.