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happyhourscience t1_j707yiq wrote

The process that resulted in Dolly was somatic cell nuclear transfer (SCNT). The process was a big deal because it demonstrated that there was a way to reprogram a cell from a "somatic" state to an earlier developmental state.

This method was developed roughly at the same time that scientists first isolated and grew human embyonic stem cells, which were isolated from pre-implantation embryos. (as an aside, mouse ES cells have been around for much longer, but hESCs proved tougher to keep going in culture).

Human ES cells are super useful in research because they can be used to generate many different cell types, which we can use to model disease and generally understand tissues that might be otherwise hard to get from humans (think neurons or heart cells).

The limitation of human ES cells is that they're hard to make with the exact genetic makeup that you might want to study. For example, let's pretend that I care about a genetic disease like Huntington's disease, which affects specific regions of the brain. If I want to study human cells in a dish, my options are limited, since getting a biopsy of the brain and growing neurons isn't going to be easy.

If you could make ES cells with a Huntington mutation, you would have a basically endless supply of human neurons, but to do that you'd need an embryo with the Huntington disease genotype.

This is where the insight from Dolly comes in: because of Dolly, scientists knew that reprogramming was possible, and a few labs set out to figure out how to do it without physically transplanting a nucleus into an egg cell. The result was the induced pluripotent stem cell (iPSC), which was a big deal and won a nobel prize. Basically, the recipe to reprogram cells using just 4 proteins was identified, and has led to a tool that is widely used around the world. Any patient's somatic cells can now be reprogrammed into iPSCs, which can in turn be used to generate all sorts of cell types to help explain the underlying biology associated with many conditions.

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Zondartul t1_j718iil wrote

So iPSCs are sort of like off-brand stem cells that can be produced without messing with embryos?

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FirstSynapse t1_j71ttjq wrote

Yes, pretty much. You can produce them from many different tissues, but most scientists (myself included) use iPSCs derived from fibroblasts (connective tissue), which can be easily obtained from a biopsy and cultured. Another main advantage of iPSCs over ESCs is that you can obtain iPSCs from patients of any genetic disease and produce any kind of cell you want to study, which will express the dysfunctions associated with that disease.

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ElxirBreauer t1_j724ftc wrote

That is a HUGE boost to research for both treatments and potential cures, I'd imagine.

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FirstSynapse t1_j727ikl wrote

It is pretty nice, and the models get better every day. As a caveat, I must say that there are LOTS of things to consider when doing research with iPSCs, mainly related to how accurately your cells represent actual human cells. For example, I work with iPSC-derived neurons and any change in the process of maturation of iPSCs into neurons vastly changes the properties of the final cells. Also, neurons and other cell types take long to mature from iPSCs. In the case of my cells, it takes around two months until they are at a stage I can use for my experiments, and they have to be maintained for that long and lots of things can go wrong.

All of this is, of course, also a problem with ESCs, but not with animal models. If human genetics are important for your experiments, iPSC models are almost the only choice you have. If there is a good animal model for the disease you're studying and organism physiology is more important, then animal models are better.

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Foreign_Implement897 t1_j724gzo wrote

So do you actually need stem cells for anything after this? Is it a complete substitute?

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FirstSynapse t1_j72b0mn wrote

If you mean embryonic stem cells, their main advantage over iPSCs is that ESCs have been around for longer and can be considered somewhat more reliable. iPSCs need to be generated in the first place from mature cells, and although this process is relatively simple (only four factors in the case of Yamanaka's Nobel prize-winning research), there is still a lot of debate over how it should be done and how it can affect the resulting phenotypes.

ESCs, on the other hand, are already naturally capable of generating tissues, so there is a larger likelihood that the resulting mature cells will resemble more the actual human ones. In studies in which the mutations of the diseases that are being studied are generated by genetic manipulation, ESCs are still preferred by many labs because of this reason.

But this is an issue for iPSCs just because it is still a very young technology, and huge advances are being made constantly that make ESCs less relevant. Being able to obtain cells directly from patients is a huge advantage as it allows to study diseases that have an important but not entirely known genetic component, like most neurological disorders.

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baumpop t1_j74uyv9 wrote

What about regrowing tissue? And does this tangentially related to the new knowledge that cells are sending information and can be "reprogrammed" (like in the anti aging studies on mice).

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aotus_trivirgatus t1_j75ysk0 wrote

When iPSCs first appeared, many people doubted that they would truly be functionally identical to ESCs. After a few years, I stopped following the field. Is the verdict in?

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Dmains t1_j70o40w wrote

Great explanation. Thank you

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zxyzyxz t1_j70z5u2 wrote

Thanks for the answer. What advancements have been made since Dolly in these fields?

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MrPsAndQs t1_j71tj9a wrote

Well, Dolly was the first mammal that was cloned, but already in the late 1950s John Gurdon used the same procedure to clone frogs.

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thismightbsatire t1_j73npxe wrote

How does the completion of the human genome project affect our ability to clone DNA?

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daaabss t1_j76cew7 wrote

Okay. Is that the simpliest explanation? Still have no clue

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EducationalCan3358 t1_j722ei3 wrote

Is this how CAR-T cancer treatment came about?

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CrateDane t1_j7297wt wrote

No, CAR-T simply uses T cells extracted from an adult. Either the patient themselves or a donor. The cells are then gene edited to express the chimeric antigen receptor, and the successfully edited cells are put back in the patient.

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saturns_children t1_j74pue2 wrote

Can this be used to create stem cells for different tissue types. For example, teeth stem cells, I know there are multiple types of teeth stem cells? And grow new teeth for example?

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Equoniz t1_j7221z8 wrote

I like how you introduce an acronym you never use, then never introduce the acronyms you do use throughout.

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