I'm obsessed with learning about epigenetics and stem cell research and this, plain language explanation, of how the Yamanaka factors were discovered is awesome!
I studied this paper for the first time in 2017 and i found it super hard to understand. Today after getting much more knowledge and experience I am able to understand it. However, I wish I could watch your video back then cuz it's super straight-forward and it explains very easily the main concept! :)
Cloning all 24 transcription factors at the time this paper came out would be quite a lot of work, so I'm sure they spent time looking through the literature to identify transcription factors that are known to be expressed early in embryogenesis.
In the Yamanaka paper, the genes of the transcription factors were delivered to the fibroblasts using lentiviral vectors. In short, lentivirus vectors are derived from HIV, but the HIV genome is essentially "gutted" to make them nonpathogenic. By doing this, the virus vector is essentially a "tool" for inserting the transcription factor gene into the host cell's genome. Now that scientists know which genes are important to cause pluripotency, there are additional ways to get those transcription factors to be expressed in cells including coaxing the cell to express these genes from their own genome.
Fbx15 is expressed in pluripotent cells but, because mice with this gene knocked out are able to reproduce, it is a disposable gene for pluripotency. The Yamanaka factors were identified in cells where a reporter gene was expressed from the Fbx15 loci. I'm not sure what else to say because your post is vague.
In September 2014, one patient suffering from a degenerative eye in Japan became the world's use of induced pluripotent stem cells (iPS) for the first treatment. www.creative-bioarray.com/Services/Custom-iPS-Cell-Services.htm
Hi, Jimmy. You raise several valid points. As a basic researcher who has very little background in translational research, I am biased toward saying that we should always do extensive research in "the dish" and in animal models before doing anything in humans. The immediate concerns over iPS cells included the fact that the "M" stands for an oncoprotein called c-myc. Moreover, the genes were shuttled into the mouse fibroblasts using retrovirus viral vectors, which have always had the caveat of inserting their genetic material into the genome in an unpredictable way. More recent work has circumvented these immediate concerns but more concerns certainly remain. Personally, I wouldn't use the word "hype" in conjunction with iPSCs since I don't think that their clinical potential has been overstated. Thanks for prompting more discussion on this topic. -Joel
I'm obsessed with learning about epigenetics and stem cell research and this, plain language explanation, of how the Yamanaka factors were discovered is awesome!
I studied this paper for the first time in 2017 and i found it super hard to understand. Today after getting much more knowledge and experience I am able to understand it. However, I wish I could watch your video back then cuz it's super straight-forward and it explains very easily the main concept! :)
Very helpful
This was very helpful thank you for making this video!
You're welcome.
Excellent. I hope I can find more of about this topic, esp. from you.
Thank you so much! Explanation about screening process was helpful.
Thanks for the comment. I'm glad it was helpful.
Thanks, great explanation, I understood almost everything not being a scientist.
Where from does this number 24 come from, I mean why not say 36 or 48 or even 1000?
Cloning all 24 transcription factors at the time this paper came out would be quite a lot of work, so I'm sure they spent time looking through the literature to identify transcription factors that are known to be expressed early in embryogenesis.
thank you
Tack så mycket, thank you i was looking for som info about this.
great stuff man.
Where do they obtain these transcription factors from? The embryo?
In the Yamanaka paper, the genes of the transcription factors were delivered to the fibroblasts using lentiviral vectors. In short, lentivirus vectors are derived from HIV, but the HIV genome is essentially "gutted" to make them nonpathogenic. By doing this, the virus vector is essentially a "tool" for inserting the transcription factor gene into the host cell's genome. Now that scientists know which genes are important to cause pluripotency, there are additional ways to get those transcription factors to be expressed in cells including coaxing the cell to express these genes from their own genome.
Fbx15 locus*
Fbx15 is expressed in pluripotent cells but, because mice with this gene knocked out are able to reproduce, it is a disposable gene for pluripotency. The Yamanaka factors were identified in cells where a reporter gene was expressed from the Fbx15 loci. I'm not sure what else to say because your post is vague.
In your video you say Fbx12 locus.
Please Sub in Spain
In September 2014, one patient suffering from a degenerative eye in Japan became the world's use of induced pluripotent stem cells (iPS) for the first treatment. www.creative-bioarray.com/Services/Custom-iPS-Cell-Services.htm
I will look into this more. Thanks for the comment.
Hi, Jimmy. You raise several valid points. As a basic researcher who has very little background in translational research, I am biased toward saying that we should always do extensive research in "the dish" and in animal models before doing anything in humans. The immediate concerns over iPS cells included the fact that the "M" stands for an oncoprotein called c-myc. Moreover, the genes were shuttled into the mouse fibroblasts using retrovirus viral vectors, which have always had the caveat of inserting their genetic material into the genome in an unpredictable way. More recent work has circumvented these immediate concerns but more concerns certainly remain. Personally, I wouldn't use the word "hype" in conjunction with iPSCs since I don't think that their clinical potential has been overstated. Thanks for prompting more discussion on this topic. -Joel