Recently, the latest achievement of Chinese scientists - through the "induction of somatic cells to cultivate human totem stem cells", was honored to nature. This is a major breakthrough, and while it may not be as sensational as Shinya Yamanaka, it is a huge improvement in the eyes of the industry (of course, there are still some problems to be solved).
Here is a summary of the content of this study:
1, This study pushes the period of induced pluripotent stem cells forward by about 3 days, so that induced pluripotent stem cells have more differentiation potential.
2, This study innovatively combines single-cell sequencing technology to help find cells with strong differentiation potential, which provides new ideas for our stem cell research.
3, there are still some deficiencies in this research, as for the Nobel Prize and the like is nonsense.
Let's talk about this long article from five aspects.
01, stem cells and stem
———————————
A person starts with a fertilized egg and eventually develops into a complete individual.
This process, in the traditional physiological sense, is irreversible.
And this process is also accompanied by the proliferation and differentiation of cells, the former is a process of becoming more, the latter is a process of cell specialization into a variety of cells, such as nerve cells and red blood cells are very different.
According to current understanding, this is accompanied by a gradual decline in the dryness of the cells. The so-called dryness here, which can be understood as potential stocks, is that the stronger the dryness, which means that the cell can differentiate into more cell types.
Among them, the fertilized egg is the strongest and can directly develop into an individual, which naturally means that it can develop into all types of cells. But like hematopoietic stem cells, they can only take hematopoiesis, and cannot develop into nerve cells.
Just like there are laymen who think that cord blood is omnipotent, that is nonsense.
So, the question is, how do you get stem cells from adults?
02, How to obtain human stem cells? ——The origin of induced pluripotent stem cells
As mentioned above, with the development, the further down, the fewer stem cells, and the weaker the stem, to adults, basically there are not many stem cells, and these stem cells are basically dry enough, can only differentiate into specific cells (such as hematopoietic stem cells), and other organs, not necessarily stem cells, such as the famous cardiomyocardial stem cells, were later proved to be fake.
But for medical biology, we need stem cells very much, short-term is scientific research, long-term that is for the benefit of mankind, think about it, with stem cells, directly want what organs have, and there is no need to worry about rejection, that is your own fall of the meat ah.
Therefore, how to obtain human stem cells has become an urgent problem. So how do you get it?
1, acquired during early human development – illegal, and may even be equivalent to killing, so it is not feasible.
2, we make a new person for it - cloning,
But this process is equivalent to going through the human race from scratch again, not only is it not ethically allowed, but the fact that human cloning has not yet succeeded may be a bit unexpected. Because in science fiction or folk literature, clones have long been the exclusive property of evil people or local tycoons. However, in fact, it is difficult to clone humans, and it was not until 2018 that we managed to clone monkeys, let alone humans.
3, can there be other means to reverse the cell and make it a stem cell?
This is what the famous Yamanaka Shinya did.
In fact, Nobuya Yamanaka was also forced.
When he was doing mice, the stem cells were rushing, after all, mice, how much is there, but when it comes to doing humans, he found that he can't find human stem cells, after all, this thing is more precious than gold.
There was no way, Nobuya Yamanaka could only solve it by himself. Eventually, he came up with the idea of reversing cells with some components specific to human cells.
This is the famous Yamanaka factor. In fact, the process, which is more boring, is to try repeatedly. Water adds more surfaces, more faces add water, and finally continues to try, a total of 4 factors are feasible.
Among them are cancer factor c-myc, transcription factor KLF4 and so on.
This discovery can be described as earth-shattering, so Nobuya Yamanaka won the Nobel Prize a few years after making this thing, almost breaking the record of the Nobel Prize for Physiology or Medicine, after all, the verification cycle of this award is very long.
03, the problem of inducing pluripotent stem cells
It seemed as if everything was perfect, and man could not help but fantasize again. But in the industry, there are still problems.
1, these factors are risky
Yamanaka factors have both cancer factors and viral factors, this thing is blunt, can only be scientific research, can not practice ah.
After all, these factors reach the human body, and if you are not careful, you will cause people to get cancer, not to mention viral factors. Therefore, All along, Nobuya Yamanaka's research has remained at the scientific research stage.
So some people wondered, can there be an easier way to do it? A Japanese female scientist began to make a big fuss and developed a new induction method, that is, to stimulate cells, such as eating some acid. After all, it's a sour girl.
She also took the name "Stimulation-Triggered Pluripotency Acquisition" (STAP), when the eyes of the world were blind, and they did not expect that sophisticated biological sciences could be so extensive.
However, it was eventually confirmed that TM was fraudulent. So her mentor committed suicide, she was invited to make a film, and she was Haruko Kohokata.
However, the process of improvement by others is still in progress, but it is much more cautious, such as adjusting factors, no matter what you say, it is also a patch.
2, this stem cell, not ok
Despite the praise for induced pluripotent stem cells, this cell, in fact, has some problems.
That is: insufficient dryness.
The pluripotent stem cells induced by Shinya Yamanaka are equivalent to the state in which the fertilized egg develops for 5-6 days, and unlike the totem stem cells, the developmental potential is relatively limited.
At this time, in fact, the cells have differentiated a lot.
To give you an intuitive demonstration, that is, IPSC, can not develop into an individual, in the body can not grow placenta.
So, scientists wonder, is there a way to make induced pluripotent stem cells a little further forward?
This is the nature of this continental scientist.
04, dry enhanced version of induced pluripotent stem cells
The nature article this time is from the Chinese Academy of Sciences and shenzhen Huada Institute of Life Sciences and other institutions
You can simply understand that the dry period of induced pluripotent stem cells is pushed forward by 3 days. The induced pluripotent stem cells this time are equivalent to embryonic cells that develop human fertilized eggs for 3 days, 2-3 days earlier than the previous Nobel Prize-induced stem cells!
Don't underestimate these few days, during the development of the fertilized egg, it is really calculated by the hour, and the difference of a few hours will make a huge difference in dryness.
Basically, it can develop into the vast majority of organs.
Because the converse inference is that 8 cells are available when doing IVF.
The reason why stem cells can develop ahead of schedule this time is actually due to single-cell technology. What is single-cell sequencing technology? It's more complex, and in general, you can understand it as a more delicate breakdown of cells.
For example, people generally think that there are only dozens of types of cells in humans, but in fact, studies have found that there may be as many as thousands. For example, even if the heart alone, there are dozens of cell types, which is the new classification method.
Not based on appearance, but based on gene expression. However, this technology is still relatively expensive, so BGI can't afford to do it, and yesterday I received a recommendation from a biological company
This time they used the DNBelab C4 platform, and then used DNBSEQ sequencing technology to sort the cells, which allowed them to pick out some of the cells with higher stem properties.
The specific process is like this
Induce the cells first, then start single-cell sequencing screening.
This is the chromatin profile that screens out the cells (it's so beautiful, I've started learning)
This is the transcriptome atlas of 4CL na ve PSC and 8CLC
Very confused, not necessary, these diagrams are for professionals to see, you just need to understand: find the potential equivalent of 3 days of fertilized eggs cells.
05, what is the problem?
Of course, there is, always remember a sentence: there is no perfect scientific research in this world.
This study also has some problems.
1, dry problems
The current stem hypothesis in this article is too ideal, in fact, the current speculation on its stem is insufficient.
In other words: many people think that the stem cells found this time are very good, in fact, these are inferences, and the article does not make an argument. So, it's a pity.
Of course, more evidence will be found in the future, and it may be feasible.
2, This article needs more verification
The conditions used this time are different from previously published papers, so it cannot be compared with previous studies, which is also the viewer's view, so there will be more research to verify.
3, the fundamental problem of induced pluripotent stem cells is still not solved
The natural defects of induced pluripotent stem cells that we mentioned are not solved in this article, so they do not have application value. However, it can provide a corresponding basis for scientific research.
So, look forward to the future.