| 1 | Elliot Nicholson | Embryonic and Induced Pluripotent Stem Cells Part 1 | 9980 | 99 | 11 | 36.3 | positive | 19:34 | Okay so welcome to this video. In this video what we're going to talk about is embryonic and induced pluripotent stem cells. Okay so embryonic and induced pluripotent stem cells so let me run through the structure of this video for you. Okay right so what we're going to start off with is discussing specialised cells. Okay and what we want to understand is what is it that determines the cell specific specialisation. Okay so you have very different cells in our body. Okay we're a multisemium organism and we have loads of different cell types that are all very different. Why are they so different? What is it that controls? Why they are so different and that's what we're going to spend a lot of time looking at. Then what we'll do is turn our attention onto embryonic and induced pluripotent stem cells. So I'll define what an embryonic stem cell is actually very early on in the video. Okay it'll take us quite a while to build up to what an induced pluripotent stem cell is. Okay but we want to look at what is it that makes a cell pluripotent. What a control makes the cell pluripotent. Okay and we'll see that towards the end. Then what we'll end up with is a discussion of the potential uses of this sort of technology in medicine in the future. Okay so we'll talk about how it can be used potentially for cell therapy, how it currently is used in genetic engineering. We'll also talk about how it's used in disease modeling and drug testing and we'll use an example of Timothy syndrome to illustrate that. Okay right so the first thing then that we want to take on is the topic of why our cell specialised. What is controlling cell specialisation? So first thing let me define what I mean by specialisation. I'll make it very clear at least what I mean by specialisation. Okay so we are a multisavular organism. We have a huge number of different cells making up our body and in different portions of our body the cells have very different phenotype. So for instance let's contrast a hepatocytes a cell of the liver. Okay so I'll draw my hepatocyte here. It's square sort of cell with its nucleus here. Okay and let's contrast this type of cell with a neuron. Okay so here's our hepatocyte and now let me draw a neuron and I'll draw the sort of archetypal picture of a neuron. So here are the denge rights of the neuron coming off the cell body and then here is the axon of the neuron and we're sure it's that particular one and there's the axon term of the neuron and here's it's nucleus. Okay so the big question that we need to start this video off with is why why are these two cells so different? Okay what is it that makes these cells so different and what is it that controls why these cells are so different? Okay so those are the two big questions that we want to discuss. What is it that makes these cells so different? Is the first question more to ask? And then secondly what controls why these cells are so different? What machinery is there in place for controlling whether a cell becomes a hepatocytes or whether a cell becomes a neuron? Okay, right. So now let's discuss a bit of development because this is going to be very, very important. We are after all discussing embryonic stem cells. Okay right so development then the early stages of development we're not going to go particularly far we're developing we're only going to go up to the blastasis stage so that being run you through how development in the human and indeed in mammals occurs. So you start off with the fertilized eggs cell here. Okay so this is our fertilized eggs cell and that's known as the zygote. Okay so here we have our zygote and then what happens is over the days after fertilization the zygote divides and divides and divides and produces a whole ball of cells. Okay however a key thing to understand here is that when it divides the cell doesn't get bigger before it divides. Okay so egg cells are absolutely enormous cells. Okay and obviously when the eggs cell is fertilized it doesn't suddenly shrink. Okay so what actually happens is this cell divides without actually growing before it divides usually when a cell proliferates. What firstly happens is the cell grows it hypertraffies and then it splits into. Okay however when this zygote divides it's just going to divide without growing which means that all the cells are going to get smaller and smaller and get to a more normal size basically. So what you end up with is this ball of smaller cells basically. Okay like so a little ball of smaller cells but the whole ball is now the same sort of size as the original zygote here. Okay now draw them on nuclei much smaller now. Okay so here are the nuclei of these cells and this ball of cells that you develop into by around the third day after fertilization is what's known as a morala. Okay so you go from zygote to a morala. Okay right then after the morala stage you develop into what's called a blastocyst. Okay and the blastocyst has two major portions so let me just show you the blastocyst. Okay so the blastocyst first he has an outer portion of cells. Okay which I'm known as the trofo blast cell was also called the outer cell mass. Okay so here are these cells making up this outer ring and it's a sphere basically. So you have the sphere of cells making up the outer surface of the blastocyst. Okay so here all their nuclei like so. Okay right so these are trofo blast cells and I might cover the trofo blast cells in in blue just a moment so these are trofo blast cells. Okay if I color those in blue here we go. Okay so this is the trofo blast you can also hear it occasionally called the outer cell mass or the trovectoderm. Okay so there are many different words that endrologists use to describe this. Okay so I'll just put that it can also be called the outer cell mass or Oc here for short. Okay so this is the outer cell mass. Okay so that makes up the outer sphere of the blastocyst. Okay but inside this sphere first you have a cavity. Okay known as the blastocyl of the blastocylic cavity. Okay but we'll just call it the blastocyl. Okay and then in the cavity what you have is a little ball of cells which we'll have here which is the inner cell mass cells. Okay and these are the cells which will actually make the embryo. Okay so this is the inner cell mass cells. Okay and sometimes you can hear the inner cell mass cells called embryo blast because they're going to make the embryo basically. So these were also called embryo blasts. Okay right so basically the embryo blast or the inner cell mass cells which are now here in orange. These are the cells which will make the entire embryo. They will make all the tissues of the body. Okay the trofo blast cells meanwhile will make the extra embryonic tissues. Okay so the trofo blast will make the extra embryonic tissues principally. The principals example of the extra embryonic tissues is the placenta. Okay so the embryo blast or the inner cell mass cells become all the tissues of the embryo. The trofo blast cells become the extra embryonic tissues. Okay so this is something important non-closure that I want to introduce you to at this stage. Okay and these are two important words that you can't really avoid if you're talking about stem cells. Okay the words totipotent and pluripotent. Okay right so what's the difference between totipotent and pluripotent or what in the first place they actually mean. Okay so totipotent is the characteristic of certain cells. Okay it's the characteristic that you can literally differentiate into any type of cell of the human body plus any type of cell of the extra embryonic tissues. So for instance I'll just put in brackets here the placenta is the key example of an extra embryonic tissue. Okay right so you don't well through your development for a very short period of time you have some totipotent cells. Okay but very quickly you lose totipotent cells. Okay so the zygote is a totipotent cell it is going to make all of the tissues of the embryo and of the extra embryonic tissues. Okay in addition the cells of the more of the are totipotent cells but as soon as you get to the bastard stage nowhere in this anymore are the totipotent cells. Okay because these inner cell mass cells they're only going to make they can only now become cells of the body. Okay and the trofer blast cells can only become tissues of the extra embryonic tissues. So none of those are totipotent anymore. So totipotent is this word that means that you can become any cell okay of the body and any cell of the extra embryonic tissue. Okay you can give rise to those cells of those tissues. Okay a pluripotent is less broad basically pluripotent is a less incredible property basically. Pluripotent means that you can become any tissue of the body you can give rise to any tissue of the human body. Okay so the inner cell mass cells are pluripotent. Okay the stem cells that are the title of this video the embryonic stem cells and the induced pluripotent stem cells they're always going to be pluripotent they're going to be able to give rise to cells any cells of the human body. Okay and they're not going to be totipotent they're not going to be able to give rise to the extra embryonic tissues. Okay right so let's now talk about what embryonic stem cells are then. Okay so this is a good time to introduce what an embryonic stem cell is and then we'll come back to the question of specialization. Okay so I'll briefly introduce you to what an embryonic stem cell is. Okay so I should mention the embryonic stem cells are quite a controversial topic. Okay people question the ethics of research with embryonic stem cells and the reason is that they are derived at least originally from human embryos. Okay but were never going to develop basically. Okay right they were developed in vitro basically. They were embryos that weren't used in in vitro fertilization. Right so where do you get embryonic stem cells from? So basically you get embryonic stem cells from taking cells of the inner cell mass. Okay so you go to an embryo at this blastocyst stage here you remove cells of the inner cell mass. Okay and then amazingly you can actually culturally cells. Okay so you can put them now on a cell culture dish. I draw a little petri dish here. Okay so we can put our inner cell mass cells on this petri dish and we can put them in certain growth mediums. Okay and we can keep them basically. We can keep them in that same state. Okay now note that doesn't happen in vivo. If you left them in the bath system and allow them to develop they would not stay as in inner cell mass cells they would start to differentiate. Okay but if you keep them in vitro you can keep them in this state basically and the key properties that they have are that they can divide and divide and divide and divide indefinitely. Okay so they have unlimited semi-division potential basically. Pralithrate indefinitely they have no hayflick limit and that's because they have the enzyme to lomerase active which will continue to extend their telomeres so that they never get down to that point where they can no longer divide. So they have no hayflick limit which is very useful in cell culture laboratories we like that. Okay because that means that you can get these things to divide and divide and divide you can propagate them again and again and again you can go from having a few cells to having a huge amount of cells you can give them to all of your friends they can make more of them and that means that we don't have to go back to another embryo and nick cells from it basically. Okay once we've got the cells then we can just culture them in vitro basically. Okay the other important thing about these endonic stem cells is that they maintain their pluripotency. Okay they remain pluripotent. Now what do I mean by remaining pluripotent? I mean what you can do is you can put them back into a blastocyst. Okay so let me draw another blastocyst here. So you go to another embryo now completely different genetic embryo and obviously you don't do this in humans you would do this in mice. Okay doing this in humans will be very bad. Okay but you can do this in mice. Okay so that's now say we're not dealing with human embryo and extem cells we're dealing with mice and brunx stem cells. So we've exactly the same principle development of mice follows the same course for this portion. Okay so we've taken in a cell mass cells we've cultured them they've proliferated fantastically. Okay now we've got some other mouse blastocyst here. Okay here are the in a cell mass cells of this one and what we can basically do is take some of our embryo extem cells here and by the way when you culture in a cell mass cells in vitro like this they're now called embryo extem cells that's what's meant by an embryo extem cell. A cell that's derived from an in a cell mass cell that we are culturing in vitro basically. Okay so what you can now do is take some of these embryo extem cells you can put them back into this blastocyst here. Okay so I'll just color this in different colors. So let's say the in a cell mass cells of the original blastocyst here are in red so these are the in a cell mass cells that actually belonged to that blastocyst. Okay but we can put in some of our embryo extem cells which came from a totally different genetically different mouse blastocyst. Okay and what we can now do is put this blastocyst inside a mother mouse and let it develop and indeed you actually get a perfectly viable mouse out of this and this is why you can't do this in humans. Okay so here we get our mouse and it's looking a bit more like a rabbit with the mind. Here's our mouse. I'll give it a tail then it'll be obvious that it's a mouse. Okay and basically what this now is is a chimera. Okay it's made out of cells that were derived from these two different populations of in a cell mass cells. Okay so most portions of the mouse will be derived from the cells of the in a cell mass that actually belonged to this blastocyst here. Okay and in fact I don't think I ever wrote to the word blastocyst I'll just put that now so this is a blastocyst. Okay right so most of the cells of the mouse will be derived from the red cells that actually belonged to this mouse's blastocyst. Okay but some of the cells of this mouse's body will be derived from the embryonic stem cells that we put in so basically to show this very crudely. Bits of the mouse will be derived from the orange cells and we can track which cells came from the orange cells and which cells came from the red cells so we can find which bits of the mouse actually came from the orange cells and you find basically the all sorts of different issues in the mouse come from the orange cells. Okay so that shows us basically that these orange cells still have the ability to make any cell of the body basically they are still purrepotent so that's why I mean by we can maintain them as purrepotent I mean that we can inject them back into another blastocyst make a chimera mouse and the mouse is perfectly viable. Okay and some of the tissues of that mouse will be made from these embryonic stem cells rather than the inner cell cells of the blastocyst originally. Okay right so that's what embryonic stem cells are. Okay right so we'll throw that aside now and we'll go back to this question of specialization okay because this is really key for understanding what these embryonic stem cells actually are we need to understand specialization okay so we're going to go back now to the question of specialization so why were we looking at development to understand specialization well basically all of these cells of the body here the hepatocytes and the neurons all of them originally come from these same cells these inner cell micellas. Okay so what we want to ask is what happens? What determines whether an inner cell mouse cell is going to become a hepatocytes or a neuron? What even is the difference between a hepatocytes and a neuron? Why are they so different is the question we want to ask? Okay so first let me give you a little bit of terminology. Okay so I want to give the terminology of specialization so specialization is the process whereby a cell like an inner cell mouse cell which at the moment can develop into any type of cell of the body actually specializes and chooses to become say a hepatocytes or a neuron okay now there's another word that people use that and it's differentiation so the process by which one of these inner cell mouse cells can choose to become one of these specialized cell types is the process of specialization which is also known as differentiation so two key words there and what we want to now understand is what is different between two specialized cells okay and what controls whether a cell is going to be a certain type of specialized cell basically | ↗ |