ESC and iPSC are almost the same

Kirill Stasevich, "Science and Life" based on the materials of Science: Reprogrammed stem cells work as well as those from embryos. 

If we compare embryonic stem cells and their artificial analogues obtained from the same source, it turns out that the differences between them are not so great. 

Embryonic stem cells have two remarkable properties: firstly, they are immortal and can divide indefinitely, and secondly, their descendants can turn into any specialized cell, be it one of the brain neurons, a liver hepatocyte or an intestinal epithelium cell - you just need to set the required molecular genetic program.

However, it is impossible to simply use the cellular material of human embryos for medical or purely scientific purposes – for ethical reasons. Therefore, biologists had to create an alternative: in 2006, Shinya Yamanaka received the so-called induced pluripotent stem cells (iPSC, or iPS) for the first time, changing the activity of only four genes; for this discovery, just six years later, Yamanaka received the Nobel Prize. 

The essence of the iPSC method is that ordinary mature cells – for example, skin cells – are converted into an embryonic state: they begin to divide all the time and lose their characteristic features necessary to perform a special function. Now, with the help of different kinds of protein shakes, they can be directed along the right path of development, so that, for example, neurons can be obtained from skin cells.

But can induced stem cells be considered exactly the same as normal embryonic stem cells? 

It was quickly discovered that there were molecular genetic differences between those and others - some genes that were silent in some cells worked in others. It can be assumed that the differences are related to the "unnatural" production of induced stem cells. However, according to Konrad Hochedlinger and his colleagues from Harvard and Johns Hopkins University, both are more similar to each other than it might seem. 

During the experiment, two lines of human embryonic stem cells were allowed to undergo differentiation, and then they were returned using the iPSC method. Then the activity of genes was compared in all of them, and it turned out that the induced stem cells were more similar in genetic activity to the parent cells than to each other. 

Differences in activity mean, in particular, that there are different epigenetic regulators in the DNA of different cells and transcription factors (proteins that activate or suppress the synthesis of mRNA on genes) work differently. In an article in Nature Biotechnology (Choi et al., A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs), researchers write that a significant proportion of such differences may be due precisely to different origins. For example, if we compare embryonic cells obtained from a female embryo with induced stem cells obtained from a man, then the molecular genetic difference between those and others may take place not because some are natural and others are artificial, but because the genes in the male and female bodies in principle work in different ways. 

However, there are still some differences: for example, 49 genes in iPSC worked differently than in embryonic cells (in total, we recall, there are 20-25 thousand active genes in humans). Two of these 49 were responsible for glucose metabolism, one for glucose uptake, the other for its cleavage. However, although both glucose genes were weaker in iPSC, the induced cells did not differ in glucose consumption and digestion from the embryonic ones. Finally, neither of them found significant differences in the main thing – in the ability to transform into cells of other types: they turned out to be equally good at producing different types of neurons, and also equally good at turning into cells of three germ leaves (from which all organs and tissues are then formed). Functionally, neither the embryonic ones had an advantage over the induced stem cells, nor the induced ones over the embryonic ones – if, again, both came from the same source and were genetically identical. 

However, there is one serious "but" here: the induced stem cells were obtained from the descendants of embryonic cells that began to differentiate in the laboratory; the donor for iPSC here was not an adult patient at all. Perhaps, in this case, the cells that were subjected to conversion to the embryonic state had some kind of molecular memory that had not yet disappeared about how they themselves had recently been embryonic. 

On the other hand, when cells are taken from an adult donor for such a procedure, after all, traces of "life experience" may remain in them, and therefore they may additionally differ from those embryonic cells from which this whole person once turned out. However, the authors themselves do not claim that different genetic origins describe all possible differences between those and others, but in some part the problem of inconsistency in genetic activity between cell types is definitely far-fetched. 

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30.10.2015