| 1 | Sciencerely | How To Make Stem Cells | Yamanaka Factors | 215657 | 6804 | 297 | 70.7 | positive | 9:32 | Hey there, before we start this video I want to thank you for all your feedback in the last weeks. Unfortunately I was not able to use my microphone and therefore I had to wait until it could record this video. But you are here, I am here and this episode is going to be awesome, so let's start. Being the son of a small factory owner in Osaka, Shinya Yamanaka was born in 1962. As a child, Yamanaka was fascinated by the smanning clocks and radios into small pieces and trying to assemble him again. He was inspired by his father to become an engineer, however as a teenager he considered studying basic sciences and then finally decided to go to medical school. He became a surgeon but felt that his skills were not as good as expected. Furthermore he also realized that many diseases cannot be cured for surgery. So Yamanaka decided to immerse himself in the basic science and stat and was introduced into the fields of STEM biology. And after some years of research his passion led to the identification of the so-called Yamanaka factors. The Yamanaka factors are one of the most important discoveries in the field of STEM science research. Through the activation of Yamanaka factors we can produce for example STEM cells from skin cells. This means that we do not necessarily need to sacrifice embryos to conduct STEM science research but we can make them ourselves. And this finding resulted in Yamanaka winning the Nobel Prize in Physiology of Medicine in 2012. Okay but what exactly are the STEM cells and Yamanaka factors? My name is Gönstaniak and today we talk about how we can generate STEM cells from our own skin. As some of you might remember we previously talked about STEM cells in this episode here. However I think we should go into more detail in order to really understand STEM cells and grasp how we can generate them. STEM cells are a special types of cells which are able to serve in you and have the capacity to produce differentiated cells. To be more precise STEM cells can generate daughter cells which are identical to the mother or which have restricted potential. Potentially is defined as the number of possible fades as cells can acquire meaning that it can change over time and become a neuron or muscle cell for example. The more restricted the potential for cell is the less fades it can acquire meaning that it might become a neuron but not a muscle cell anymore. We call the process in which a cell becomes more restricted differentiation. Generally speaking we can distinguish between embryonic and adult STEM cells. Of course we only find embryonic STEM cells very early in development. Embryonic STEM cells can become a lot of different cell types and therefore we call them pluripotent. Adult STEM cells on the other hand are found throughout life and they are generally more restricted than embryonic STEM cells. We call them multi potent if they give rise to several cell types and unipotent if they produce the same cell types over and over again. Hematopoietic STEM cells are found in bone marrow and they are a great example for multipotent STEM cells as they give rise to all different components of the blood. On the other hand we also find unipotent STEM cells in our liver and they are the reason why our liver is able to recover after long night out. By now you might have realized that the potency of STEM cells generally seemed to decrease with development. While during early development STEM cells might become all kind of different cell types such as skin cells, neurons or muscle cells. Adult STEM cells are generally more restricted and might give rise to different components of the blood for example. This restriction however is very important as STEM cells might otherwise form what we call teratomas in our body. Teratomas are cancer like structures which could rise to all kind of weird different tissues. And teratomas might find teeth or hair where we don't expect them and to keep your appetite I will not include a picture of teratomas in this video. Oh man, I love this topic. So let's go on, we've discussed the two major characteristics of STEM cells. But here are some interesting thoughts. Embronic and adult STEM cells have the same genetic information as most other cell types in our body. So why do only STEM cells divide and give rise to these different cell types? And more importantly, can we also force differentiated cells to become STEM cells? We could actually spend hours trying to answer these questions and we also must realize that only a small fraction of STEM cell biology is understood. But very broadly speaking, STEM cells activate unique genes which are not activated in differentiated cells of our body. A lot of these genes produce so-called transcription factors, transcription factors are proteins which on the other hand activate many other genes downstream. In this way we can control the activation of many genes through only some transcription factors. Of course there are many other ways to influence STEM cells but we will not go into much further detail. But the important point is that some genes are only active in STEM cells and they are also required from maintaining their characteristics. So what happens if we also activate these genes in other body cells? Well, this question was answered by Shinya Yamanaka when he discovered and activated the soul of Yamanaka factors in fibroblasts which are found in the skin. And just to clarify, Yamanaka factors are four genes named Octophy4, Sox2, KLF4 and Cymic. These genes all influence the activation and inactivation of other genes. The amazing fact about Yamanaka factors is that they are not only very important for STEM cells but can also be used to generate STEM cells from differentiated cells. This means that we can reprogram cells to become STEM cells and in this regard we call an induced pre-reported STEM cells or IPS cells. And it was the identification of Yamanaka factors and the generation of IPS cells for which Yamanaka got a Nobel Prize in Physiology or Medicine. At this point it also makes sense to take a closer look on what kind of experiments Yamanaka conducted. In the beginning of the century his goal was to identify which genes are important for maintaining pre-repotency. And so he and other scientists started to identify genes which are highly active in STEM cells. But then in 2006 he wanted to see if some of these genes are not only important for maintaining pre-repotency but can also convert fibroblasts into STEM cells. And therefore he started to read a lot and he identified 24 candidate genes which might be important in his context. He then started to genetically change fibroblasts to become resistant against a certain drug if they are STEM cells. This means that these cells will only survive the exposure to the drug if they become STEM cells. He then fused the 24 candidate genes with parts of viruses in order to infect the cells. As a consequence they introduced genes become activated and Yamanaka saw that indeed after a while fibroblasts became STEM cells. But it didn't stop here since he thought that not all 24 candidate genes are equally important to make STEM cells. He then infected fibroblasts with different combinations of these genes. And this is how he discovered the Yamanaka factors. If anyone of you wants to become a researcher or is interested in STEM cell biology I provided you the link of the original publication in the description. I think it's a very great publication. Okay so we can now isolate fibroblasts from our skin and convert them into induced brew-putting STEM cells. But why is this important? The numerous different positive applications of induced brew-putting STEM cells. We can use them for example to generate tissues or organs. And this is a very important topic. In Germany for example the number of postmortem organ transplantations has declined by over 30% in the last 10 years. Induced brew-putting STEM cells have the potential to generate tissues or organs for transplantation. I also want to point out that these tissues or organs could be very compatible with the recipient if they derive from the patient's own cells. If you're interested in current advances in generating tissues or organs let me know in the comment section and we make another video about this. Induced brew-putting STEM cells have great potentials in clinical applications. However they also have one major drawback, the risk of developing cancer. You see, STEM cells and cancer cells show many similarities as they are both able to undergo extensive proliferation. Moreover many of the genes which are active in STEM cells are also active in cancer cells. For example one of the Yamannaka factors, CIMic is a proto-oncocene. This means that CIMic can provoke cancer if it is highly active in a cell. In the case of CIMic researchers have adapted Yamannaka's protocol in order to make this dangerous gene redundant. In Yamannaka's original publication the candidate genes were introduced into the cell by using viral components. Since these viral components can integrate into the genome that can cause damage or provoke cancer. Therefore we still look for the best alternative way we can use for example RNAs which do not integrate into the genome. But nevertheless in 2014 the first clinical trial using IPS cells was launched. Here in these probed in STEM cells were generated from a patient who suffered from macular degeneration which is the main cause of vision loss. These IPS cells were then transformed into a retinal pigment epiphylose cells which were then transplanted into both eyes of the patient. And the therapy was actually quite successful, the degeneration of the patient stopped and the vision improved. And so clinical trials in other fields such as heart disease that beat this Hispanic cord injury are in progress. If you are interested in these similar topics let me know in the comments section and leave a like. And don't forget to subscribe and hit the bell button in order to stay informed about the greatest discoveries in life sciences. And with that I'll see ya. | ↗ |