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Skip to 0 minutes and 11 seconds Today we are going to see the genome in action; our body, our diversity, our unity… One genome, many cell types and how this works, but also how the development from a single cell to a full individual proceeds. We are going to take this information also to define and to understand the interest we may have in what is called «stem cells». One of the interesting issues of biology is how a single genome may be at the base of all the cell types of our body.

Skip to 0 minutes and 52 seconds We all come from a single sperm, from a single egg, from a single cell that was at the very beginning of the divisions, Two, four, and so on, and how this cell, division after division, gets more specialized. The basic idea of that is that the genome is the same in all parts of our body, but different parts of the genome are at work in different cell types in different parts of our body. So, we have a whole world of what we call genome regulation, which will work continuously during life and will make some parts of the genome be at work and some parts be repressed.

Skip to 1 minute and 55 seconds If we look for example at our arm, we are going to see many different kinds of cells,

Skip to 2 minutes and 3 seconds extremely different kinds of cells: from the bone to the nerves, to the vessels, to the muscles… We have around 250 cell types in the human body and if we look only at the case of immunity, the cells, the white cells in our blood, we are going to see dozens of cell types again. In this case, in immunity, we know precisely which specific genes are in action, are being used to differentiate these cells in specific cell types. So, the basic idea is that we all come from a single undifferentiated cell and this cell divides many times to make our billions and trillions of cells, using parts of the genome.

Skip to 3 minutes and 5 seconds And this process is called “cell differentiation” in which from a very generalized and undifferentiated cell will come millions of strongly differentiated cells which are very different from the morphological and from the functional point of view. In fact, if we look at our cells, we may make the difference between what are the somatic and the germ cells.

Skip to 3 minutes and 39 seconds Our body is made of what we call somatic –“soma” means body– and we have a very special kind of cell, the “germ cells”, that are the ones that are at the base of reproduction, meaning that we always have to make the difference between what happens in ourselves, in our body, in our “I” and what happens to these specific cells –the eggs in women, the sperm in males– that are at the base of producing new individuals. And the difference is important in the sense that the somatic cells will have the standard amount of DNA, the standard amount of chromosomes; but the cells that will be at the base of reproduction have one half.

Skip to 4 minutes and 33 seconds We usually call them “haploid” and “diploid” numbers of chromosomes. The idea of our genome is that there are many ways in which the genome will have this very strong and precise regulation.

Skip to 4 minutes and 57 seconds A very interesting part of that is what is called the epigenetic: modifications that are reversible on a cell’s DNA –or sometimes in the proteins attached to the DNA called histones–, which affect the gene expression without altering the DNA sequence. These are the “epigenetic marks” of the DNA, meaning that the sequence is a given one, but the information is “do work” or “do not work”; “make RNA a protein” or “do not make anything”. For example, in a given place, the DNA is really very well structured around the proteins we call histones. And sometimes there is space between these compact zones. If there is space, it’s possible that this sequence will be used, but if it’s compact it cannot be used.

Skip to 6 minutes and 9 seconds Here we may see the differentiation between a hepatic cell and a brain cell just because a single gene may be expressed in one of them and not in the other. So, we have a new level of information in the DNA which is not just in the sequence it has, but in when and how it will be expressed. One of the most well-known of these epigenetic marks is called the “methylation of cytosine”; cytosine is one of the four blocks of DNA, and when there is this methylation, it alters the general pattern. In general, these epigenetic marks are inherited within the somatic divisions. When a cell begins having these marks, it will reproduce into other cells that will have the same one.

Skip to 7 minutes and 18 seconds But when making reproductive cells, this will be, most of it, erased. The idea, then, is that these epigenetic signals may repress a gene and in some cases, it’s very well known that this methylation makes the DNA to be really packed and when it is packed it cannot be functional. An interesting example of that is to look at sex chromosomes. Males are XY, females are XX. The “X” chromosome is a normal chromosome, big and with many genes and the “Y” chromosome is tiny with just a few genes to produce the single trait of being male. The question is how do women handle the double dose of the X chromosomes? Because, in fact, it has double the amount of information.

Skip to 8 minutes and 26 seconds The idea is very simple: there is the inactivation of one of the X chromosomes in females, and when a cell makes the decision of which of these two chromosomes gets inactivated, all the descendants will have the same one inactivated. In general, however, a woman will have one half of the X chromosomes coming from her father and one half of the chromosomes coming from her mother inactivated.

Skip to 9 minutes and 0 seconds We can see that very easily in the case of cats: when you see a cat with two colors, it’s always a female because sometimes it has inactivated the X chromosome which makes the color of the fur black or brown. This regulation may come also from external input. The best known case is how hormones –steroid hormones is a very nice example– are activated. The activation comes straight from the DNA and regulates the gene expression of passing on sets of genes. What we have seen is this process of differentiation of cells through genome regulation.

Skip to 10 minutes and 4 seconds We can ask ourselves: if this process of differentiation could go back, could one of the cells of my brain or my muscle go into the undifferentiated state? And the answer is no.

Skip to 10 minutes and 23 seconds But, there is an interesting point: there are undifferentiated cells in all tissues and these are what we call the “stem cells”. And one of the hot issues in biology is to force this de-differentiation .

Skip to 10 minutes and 47 seconds In the embryo, each of the cells is what we call totipotent: it can give from the single cell to the whole individual. But during the process, it will go differentiating and lose this overall potential of giving all kinds of cells. And here comes the concept of «stem cells» that are undifferentiated cells that can differentiate into specialized cells and can divide to produce more stem cells. So we have a set of… total potential lost through differentiation. So, a stem cell is a cell that could give rise to other cells, other stem cells, and differentiate into any kind of cells in our organism. This is the interesting part because these stem cells are being used in biotechnology today.

Skip to 12 minutes and 4 seconds There are two main classes of stem cells

Skip to 12 minutes and 7 seconds that are being used in lots of experiments: on the one side, the embryonic stem cells, that are formed as a normal part of the development of an embryo and can be isolated from the embryo and grown artificially. These cells can produce any kind of cell in our body. But in recent years, we have been able to induce fully potent stem cells that are created artificially in the lab by reprograming a given patient’s own cells. This is very interesting because you can take cells from the skin and make them go back in this process of differentiation and then try to reprogram the differentiation and go into any kind of cell that exists in our organism.

Skip to 13 minutes and 11 seconds Of course, there are lots of diseases and conditions where a stem cell treatment is promising and emerging. So, what we have seen is how cells regulate, the expressions of specific parts of the cell, specific parts of the genetic information at work and how these cells are going from the general zygote to be very well differentiated, and how nowadays we are trying to go back on that to make what is going to be in the future stem cell therapy.

The genome in action

We shall see from one genome we can have many cell types; the difference amongst somatic and germ cells; epigenetics and aterm cells. How can a single genome may be at the base of all the cell types of our body?

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Why Biology Matters: Basic Concepts

Pompeu Fabra University Barcelona