Why does this happen? Why can't the the ES cells just differentiate into the cells of the tissue into which they have been injected? Why all the 3 germ layers and not just one? Why do they proliferate so much out of control and generate a tumor?
Sorry for the many questions but this is quite unclear to me...
So this is of course by nature all philosophy and rationalization, not science... but I'll try.
ESC are built to become proper tissues during embryonic development. If you throw them into a fully mature tissue, the signals it's going to be seeing are going to be very different from what it would be seeing during normal development. So at least it seems to make sense that they would be confused in some way. You're putting them into an environment that's very different from anything they'd ever naturally encounter.
Not every ESC forms a tumor. You can even deplete the tumor-forming subpopulation with surface markers. So that looks more like dysfunction. There are only
You may mean different things by the term "tumor". Teratomas are considered a tumor because a mature organism should not develop a mass with three germ layers unless , but that is exactly what you expect ESCs to do. I don't believe this has to do with a tumor-forming subpopulation, but I could be wrong.
The reason why these cells will form the three germ layers is that development is very conservative about signaling molecules. Despite the extreme complexity of development at >400 cell types, there are only a dozen or so major morphogens that govern spatial-temporal patterning. This means the function of the morphogen depends on the state of a given cell otherwise there would need to be hundreds or thousands of independent signaling processes during development to avoid overlap. Therefore, the effect of developmental signals also depends on the state of the cells being exposed to that signal.
By injecting your cells, they will be exposed to the specific signals within the tissue, but the developmental outcome in your ESCs will be totally different than the outcome of the somatic cells in the tissue you inject into.
The ES cells are put in environment with some differentiation factors and lack of LIF (for mouse) or bFGF (for human). So they start forming an embryo as they continue their developmental program. Due to absence of proper regulation the formed teratomas have some stochastically differentiated cells representing all germ layers.
Hello Paolo,
I would like to give a direct and brief answer.
During normal development, ESCs are destind to form three germ layers which form a complete organism at later stage and when you inject them in vivo they simply do what they are expected to do. They don't differentiate into cells of tissue in which they are incorporated because the paracrine signals are not strong enough to revert them to a direct differentiation into concerned tissue type.
They proliferate unlimitedly because they have potential to give rise to almost all cells of body (except-extraembryonic part, placenta) and can go through huge number of population doublings and hence unlimited proliferate .
Anything which is proliferating too much is going to form a tumour ultimately and because they are ESCs which are destined to form three germ layers so they generate a tumor with three germ layers which is called teratoma.
Hope it helps!
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