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Cellular specialization (differentiation)

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Visit us (http://www.khanacademy.org/science/healthcare-and-medicine) for health and medicine content or (http://www.khanacademy.org/test-prep/mcat) for MCAT related content. These videos do not provide medical advice and are for informational purposes only. The videos are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen in any Khan Academy video. Created by Vishal Punwani.

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  • piceratops ultimate style avatar for user ursula.m.anders
    What happens to the daughter cells that do not have any or have very little transcription factors? Do they remain stem cells?
    (21 votes)
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  • hopper jumping style avatar for user Yuya Fujikawa
    At , I thought stem cells are totipotent?
    (4 votes)
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    • piceratops ultimate style avatar for user Darmon
      The only totipotent (capable of becoming any human cell) cells are the cells of the morula, which is the small mass of cells formed by the first few mitotic divisions after zygote formation. From the blastomeres (embryonic stem cells) onward, human stem cells are only capable of being pluripotent in their least differentiated form. :)
      (9 votes)
  • leaf green style avatar for user Isabel Johnston
    What is the Inner Cell Mass?
    (3 votes)
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    • leafers tree style avatar for user Christine Delligatti
      This is highly simplified but here's the most basic answer:

      After a few days of division, the zygote is now what is known as a blastocyst. There are approximately 32 different cells, and 16 form a sphere shape on the outside and 16 form a 'mass' on the inside. The outside is called the 'trophoblast' and the inside is called the 'inner cell mass' because it resembles a little bunch of cells bundled in the corner. The inner cell mass is what could one day develop into a baby (permitting it properly implants and the pregnancy is not terminated on purpose or environmentally). This means all of those 16 cells contain the ability to differentiate into all of our different body structures!

      Interestingly, I learned last semester in my Anatomy II class that this is also the stage where (identical) twins/triplets/whatever are differentiated. Just something to think about! It's crazy to me that it happens days AFTER fertilization!
      (8 votes)
  • old spice man blue style avatar for user mand4796
    Are HOX genes a type of transcription factor?
    (3 votes)
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    • female robot grace style avatar for user tyersome
      HOX genes encode proteins and those proteins are transcription factors.

      This may seem excessively fussy or pedantic, but it is really important to be clear that —
      genes are regions of DNA that encode RNA molecules. If the encoded RNA is a messenger RNA (mRNA) it may then be translated into a protein.

      These proteins can have one or more functions — in the case of the proteins encoded by HOX genes they help control development by influencing the transcription of other genes.
      (5 votes)
  • boggle yellow style avatar for user Zoe LeVell
    How are new red blood cells created if they don't have a nucleus?
    (3 votes)
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  • aqualine ultimate style avatar for user HiHi1212
    Hmm... what about cancer cells? Are they still developed from stem cells?
    (3 votes)
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  • starky tree style avatar for user DoulosChristou5
    How is this kind of development regulated? I don't understand.
    (4 votes)
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    • winston baby style avatar for user Ivana - Science trainee
      It is regulated by gene transcription and external environment as well (explained in the lesson).

      Basically, what genes are turned on or turned off, is responsible for the final product - what type of cell you will get in the end.

      There has been done study in Drosophila melanogaster:
      cell specialization depends on a pair of proteins that act as super regulators of proteins that were already known—one super-regulating protein encouraging a cell to differentiate and the other trying to hold back the process.
      They are so-called Helix-Loop-Helix proteins, "master-regulating" proteins.
      Successful cell differentiation requires the presence of both master-regulating and super-regulating proteins.

      (2 votes)
  • aqualine ultimate style avatar for user meldiggy21
    Isn't the cell at a heart cell?
    (3 votes)
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  • blobby green style avatar for user siddh.p.bamb
    What effect do transcription factors have on differentiation?
    (3 votes)
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    • female robot grace style avatar for user tyersome
      Transcription factors are involved in the control of most processes in cells — this includes differentiation.

      Since there are thousands of transcriptions factors (e.g. more than a 1600 transcriptions factors in the human genome) it isn't possible to say the effect of "transcriptions factors" as a class on differentiation — they have many roles.

      One example, the proteins encoded by HOX genes are transcription factors — they help control development by influencing the transcription of other genes that are involved in segmentation of animal bodies.
      (See for example this wikipedia article:
      (1 vote)
  • male robot donald style avatar for user cktang88
    At , what happens if multiple groups of cells try to induce the same group of cells to do different things?
    (2 votes)
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Video transcript

- [Voiceover] You've probably heard of stem cells by now. You probably know that every cell in our body, whether it's a muscle cell or a nerve cell or a skin cell or a red blood cell, or any other type of cell really, they all came from a common group of stem cells during development. All of these really, really specialized cells like this muscle cell here with its little contractile proteins, and this nerve cell here that can send signals, and this waterproof skin cell here, and this red blood cell that carries our oxygen, all of these came from these stem cells up here, which were completely unspecialized. How does something like this happen? It's actually pretty interesting. Let me first give you an analogy here. Just imagine a library, right, like the one you used to go to when you were a teenager or something like that, and the one that you hopefully still go to. It has all the books you can imagine, right, but depending on which books you borrow and which books you read, you are changed. You end up knowing a totally different subset of stuff compared to someone who read different books than you, right? But all the books that you both read are still in this one library. There's actually a really similar system with our genes and with our DNA. Recall that inside the nucleus of each cell is your DNA. This is our library, this is our set of genetic instructions for building our entire body. Within our DNA library here we have our books, which are segments of our DNA that we call genes. Genes give our cells specific instructions on how to make different kinds of proteins. Having different proteins around, that changes the way our cells look and it changes the way our cells act so it gives our cells really different abilities. What I mean with the exception of the red blood cells which lack nucleii, every single somatic cell in your body contains the exact same DNA. Yet this muscle cell here, right, it looks and it acts differently to this neuron here. That's because they're each reading different books in our DNA library. They're using different genes to make their proteins. Just a bit of terminology here, when a cell is actively using certain genes, it's said to be expressing those genes. A gene being expressed is said to be turned on, and one not being expressed is turned off, so just keep that in mind. Why am I telling you all of this? Because in the end it all relates to how our stem cells all the way up here end up differentiating into our specialized cells down here. The bottom line is in order to differentiate to, for example, specialize into our muscle cell here, this stem cell up here turned on its muscle cell genes. Here's its DNA and I'm highlighting its muscle cell genes that it turned on right now. It also turned off some other genes. By turning on its muscle cell genes, now proteins get made within the cell that changes how the cell looks. See now it's a bit elongated, right, this muscle cell here. It also changes its functions. Now our muscle cell has contractile proteins in it to help it be a nice useful muscle cell to help us move around, right? Now our neuron here, our stem cell turned on its become-a-neuron genes here, right? It turned off some other ones, and then the cell started producing all the proteins it needed to turn into a neuron. Like the proteins that would make it elongate like this and grow out these little spiky things up here called dendrites, okay? Let me also say that remember our stem cell up here was pluripotent. It could turn into any of our somatic adult body cells. But once it's specialized into these mature cell types, these can't go on to differentiate into other cells. They actually can't de-differentiate either. They can't go backwards up to stem cells naturally, at least in us humans. So these cells stick around to form our bodies. By now you must be wondering what determines what genes in the given cell are turned on or off? In other words, how the heck does this cell know it's time to specialize into a different cell type? It turns out that cells decide what they're going to grow up to be based on cues they get. These cues can be from their internal environment or their cues can come from their external environment, their outside environment. Let me just show you two major ways this can happen here, these cues. In the development of lots of different organisms, us humans included, we start out with one cell, right, the zygote. Our zygote has these little proteins called transcription factors floating around in its cytoplasm. Also the precursors of these transcription factors are there too, little bits of MRNA. Two things to note. First, transcription factors will activate certain genes and turn them on. That's what transcription factors do. Second, notice that all these little transcription factors are clustered around in one area. This is important because when the zygote starts to divide, where do all these transcription factors end up? Like you see here, they only end up in the cells that divided off in that original region where they all were clustered around, right? So these cells up here don't have any or don't have much, and these cells down here have a whole heap of transcription factors. Now you can imagine that different genes will get activated in these different cells. That'll determine what each of these cells specializes into because now they're gonna make different proteins. This mechanism here is pretty appropriately called asymmetric segregation of cellular determinants. It's this big mouthful here but if we break it down here, you can see asymmetric because it really just refers to how these transcription factors are not symmetrically distributed among the daughter cells here. This cellular determinants bit is just referring to the transcription factors or their precursors. That's one way that cells can be made to specialize into different things, just having different transcription factors around. But the second way to specialization that I'll mention is called inductive signaling or just induction. Induction is kind of like really strong encouragement, almost like peer pressure, where one cell or actually usually a group of cells can induce another group of cells to differentiate by just using some signals. The signals could be passed a few different ways so they could be passed by diffusion. They could be released from one group and just diffused over to the other group where they'll bind receptors on the other groups and cause the cells over there to differentiate. Or the induction could be done by direct contact between cells, right? You can see these little surface proteins on each of these cells binding each other. That's direct contact. Or you could have signals passed through gap junctions, which are little connections, or actually I should say connexons between cells that are connected and that could induce the cell to specialize, this cell over here. I called this a connexon because in cellular biology, these proteins that make up part of a gap junction are collectively called a connexon. Anyway, induction is absolutely key in forming lots of our body parts, like our limbs are formed by partially through induction. Our ears and our eyes and lots more of our body parts are formed through induction in development, in embryological development. So induction is really important in cell specialization. On that note, I'll just remind you remember the goal here with the cytoplasmic determinants, those transcription factors I talked about earlier and then all these signals that you get in induction, remember the goal is to get cells to change their gene expression, right? To flick on or flick off certain genes, which ultimately is what causes cells to differentiate into other more specialized cells.