And the first Nobel Prize of the year has been awarded! This year, the Nobel Prize for Medicine and Physiology has been awarded to Sir John B Gurdon and Shinya Yamanaka for
“for the discovery that mature cells can be reprogrammed to become pluripotent”
So what does this mean?
All cells in the human body originate from stem cells, but what is a stem cell?
The scientific definition of a stem cell, is a cell that is capable of producing another stem cell, and a less potent progenitor. This means that when it divides, it produces another stem cell like itself, and another cell which has less potential in what sort of cells it can divide into.
When the fertilised egg which was going to develop into the human being you now call yourself first started dividing, it divided into a population of stem cells. These stem cells had the capability to become any cell in the human body. The name for this capability in a stem cell is ‘totipotent’. The same stem cell could have produced a neuron, or a sperm cell, or a white blood cell. The precise, local chemical environment of the stem cell then caused it to specialise into a different, more restricted stem cell. This stem cell could perhaps only form different cells from the same organ, like the different types of neuron or glia which make up the brain. These stem cells, in response to their chemical microenvironment, would have divided and divided, and become progressively more and more restricted in their cell-producing potential that we end up losing the all-producing-stem-cells from our embryonic phase.
As the above diagram shows, there are many different types of stem cell, and they fall into different levels of the potency heirarchy depending on how far along development the organism is;
- Totipotent - The first stem cells formed from the fertilised egg are totipotent stem cells. These are capable of producing any cell in the body - both embryonic cells and non embryonic cells.
- Pluripotent - The majority of the totipotent stem cells eventually become slightly more restricted in their cell-making potential. Pluripotent stem cells can produce most cells in the body, but no embryonic cells.
- Multipotent - From pluripotency, the potential becomes even more restriced. Multipotent stem cells can produce cells of a particular type of tissue. Like neural stem cells can produce any of the many different types of cell present in the nervous system, but they can’t produce cardiac muscle cells
- Unipotent - Are the most restricted type of stem cell. Unipotent stem cells can only generate one type of cell, but are regarded as stem cells as they can produce other unipotent stem cells.
Fast forward to adulthood and you have probably lost the vast majority of all your totipotent and pluripotent stem cells. Each organ will have a limited supply of local stem cells, likely multi- or unipotent, to allow for limited regeneration of cells.
Pretty much all of our cells contain the same DNA. Yet they are different. How does a stem cell become more restricted in what it can produce?
It’s done by genetic switches. All cells in the human body will contain the same genetic information (barring the egg and sperm, but they’re special), but will be vastly differ from one another. Look at neurons and muscle fibres, for example. This is achieved by expressing a particular pattern of genes. Some genes are switched off, and some genes are switched on. This produces various patterns of genetic expression, and it is this which produces the distinct cells which construct our various tissues and organs.
Different types of muscle fibre and neuron. All originate from the same totipotent stem cells, all contain the same DNA (within the same organism). In each different cell, different genes are switched on and different genes are switched off. these switches were determined by specific chemical signals in their microenvironment during their production from stem cells.
The original totipotent stem cells in the embryo would have responded to chemical cues in their microenvironment which would have signaled for them to change into more restricted pluripotent stem cells. These pluripotent stem cells would then have responded to different chemical cues to become even more restricted multipotent stem cells, and so on. The chemical cues would bind to receptors on the surface of the cells (or receptors within the cells), and these receptors would have signalled to the cell to switch on certain genes, and switch off other genes - producing the correct genetic pattern for that time and place.
A. Are different types of chemical cues; B. Is a receptor; C. Is the Cell; D. The Nucleus; E. The genetic material within the nucleus, aka the DNA.
The diagram shows how chemical cues can induce genetic changes. They can bind to the receptor, and the receptor initiates a cascade of biochemical pathways within the cell to affect the genes, OR the chemical signals can pass through the cell membrane and directly affect the DNA itself.
With regards to the nobel prize, these scientists figured out how to reverse engineer these signals to turn restricted cells back into pluripotent cells - potentially allowing us to generate helpful stem cells from any other cell in our body. Stem cells can be hard to come by, but now with a method to actually produce them in the laboratory from easily obtained resources, we’re on track to better understand debilitating disease processes, and may even be able to adapt this technology for use in regenerative medicine.
Congratulations, guys! Well deserved!