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Stem Cells

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Cells in our bodies have the same amount of DNA, and that DNA is completely identical! So how come a muscle cell and a brain cell both have very different structure and function despite that? How can cells be different to one another yet carry the same genetic information which codes for the same proteins? Indeed, how come most of a cell’s DNA is not translated?


The answer is that only the relevant genes are active in a given cell at a given time. The rest are inhibited because their transcription and/or translation is switched off. So how do cells become specialised?


Totipotent Stem Cells


Stem cells, just like tree stems are to branches, are the common source of all different kinds of cells. Cells start out as stem cells, and totipotent (totally-powerful) cells can differentiate into any kind of cell. When they translate only certain parts of their DNA, they become specialised.



Pluripotent (many-powerful) stem cells can differentiate into a wide variety of tissues, but not quite any whatsoever, like totipotent stem cells.



Multipotent stem cells are yet another sub-branch, narrower than pluripotent stem cells. End-point specialised cells such as heart cells are therefore unipotent and can only propagate their own type.


Embryonic stem cells form the mesoderm which is a yet-unspecialised layer of cells that go on to form a variety of different tissues and organs including the heart, develop into precursor heart cells called cardiac progenitor stem cells which go on through further stages of specialisation in the fetus and adult before reaching their end-point unipotent state.


Differentiation is driven by specific proteins and signals at different stages, delivered in specific doses to induce the right changes at the right time.



The embryos of mammals possess totipotent stem cells which upon differentiation and development into the adult organism do not occur again. The adults only have multipotent stem cells which have a limited range of cells they can change into. Using totipotent cells from embryos poses ethical issues because the embryo is destroyed in the process. Additionally, a source of disposable embryos must exist to provide the source for these cells.


Adult plants, on the other hand, retain many totipotent stem cells and that’s how you can actually grow a whole plant in vitro from just a cut fragment of any part of the plant. The conditions can even dictate which organ will develop!


Therapeutic Potential


The benefits of being able to grow any kind of cell from a stem cell (totipotent or multipotent) are vast. Replacing damaged tissue in heart failure and cancer is one example. Genetic disorders such as Type I diabetes could also be addressed by stem cell therapy in the near future. Deafness, blindness and infertility are also on the list of conditions that could be treated by stem cell therapy.


The same signals known as protein transcription factors which enable differentiation in organisms can be used artificially in the lab to grow and differentiate different types of cell.


The transcription factors dictate which proteins get made from the DNA, which in turn determine the structure and function of the cell. In this manner, already differentiated cells like fibroblast cells (whose function is synthesising the cell extracellular matrix) can be coaxed into reverting to a stem cell-like state and then be used to differentiate again into a different type of cell such as a neurone. The new stem cells made this way are known as induced pluripotent stem cells (iPSC). They do not pose the issues that embryonic stem cells pose, because the source of cells is not an embryo.


Here is what the path of fibroblasts to iPSC looks like:



Fibroblasts are cultured in nutrients at 37 degrees Celsius. Retroviruses, which can infect fibroblasts, are used to deliver several transcription factors to the fibroblasts. These transcription factors are Oct3/4, Sox2, Klf4 and c-Myc. They dedifferentiate (revert) the fibroblasts to a stem cell-like state comparable to embryonic stem cells, hence producing iPSC. These can be cultured and used with a yet another different set of transcription factors to differentiate into specialise cells like heart cells.


Oct3/4 and Sox2 are involved in cell self-renewal which is what enables potency as opposed to specialisation, while Klf4 and c-Myc are involved in regulation cell proliferation and death (apoptosis), differentiation and reprogramming. Research is constantly discovering new transcription factors and combinations of these that have roles in various cell activities at different times in development. Therefore transcription factor cocktails can be figured out for different purposes such as differentiating neurones.


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