Topic: IPSC-plus for the masses...

Did you ever want to grow replacement organs, tasty steaks, or sex partners in your basement from a cheek swab?   Well, welcome to the biohacking forum, which is, in fact, about just that.

We have no idea if vatgrown autocannabalism actually is vegan, but hey.

Step one is to revert your own stem cells - to take cells that aren't stem cells, such as your cheek lining, and turn them into cells which can do anything.  And we plan to do this with stuff that would be off-the-shelf to the average mostly-broke homeless person, or suitable for stem-cell therapy in a post-civ catastrophe in the 'survivorman-of-indeterminate-gender' phase.

Yamanaka Factors

The first reprogramming to pluripotent stem cells was undertaken by Shinya Yamanaka (Kyoto University, 2006).  By removing genetic manipulation from their full list, they found the four minimum genes required to revert a cell to a pluripotent stem cell.

Oct4 : Oc3 is equally effective, while the rest of the Oct family is not.

Sox2 :  Sox1 is equally effective, while Sox3, Sox15, and Sox18 work, but with decreased efficiency.

cMyc :  totally a carcinogenic oncogene.  nMyc and lMyc are equally effective.

Klf4 : Klf2 and Klf4 are equally effective.  Klf1 and Klf5 work, but with decreased efficiency.

Later efforts found that selecting for Nanog activation rather than Fbx15 activation induced by the Yamanaka factors created cells indistinguishable from embryonic stem cells, as opposed to "just some half-assed stem cells that are sort of cool."

OTC Transcription Simulators

Yamanaka's work, iirc correctly, involved inducing transcription via GMO-viral infection.  This changes the threat profile from "occasionally, your biocompatible organ spits off cancer cells" to "your biocompatible organ infects you with a virus that will make every cell in your body spit off cancer cells."  Not great.

Luckily, Deng et al (Beijing University, 2013) managed to epigenetically reregulate cells to induced pluripotent stem cells using only a cocktail of seven various small molecules.  I've... got some reading to do, but as far as I can tell, none of them fit the "neo-caveperson" hacker ethos.... yet.  I'll get on that.  Good news, however, comes from Melton's 2008 work.

The HDAC (histone deacetylace) inhibitor Valproic acid not only works, but is 100-fold more efficient than Yamanaka's transcription factor abuse.  It is hypotheosized to mimic cMyc.

This isn't yet good for our "neocaveperson/everyone/no entry barrier" method, because, well, prescription-shopping is hard enough for our Trans* friends.  Luckily...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559235/
https://www.ncbi.nlm.nih.gov/pubmed/16373710
https://www.ncbi.nlm.nih.gov/pubmed/27742468
https://www.ncbi.nlm.nih.gov/pubmed/26859163
https://www.ncbi.nlm.nih.gov/pubmed/30252114

...butryic acid is an HDAC.  And it's produced in...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063406/

...the colon.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646248/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116817/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823506/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928258/

Largely as a response to gut bacterium chomping up resistant starch, of which cold oats are one of the richest foods, followed by green banana flour.  If you're familiar with fermenting human sewage under water for methane production, just take a crapload of oats, run an aquarium bubbler for an air stream, have a little sodium bicarb in the outlet air filter... and you'll be producing a decent technical grade of sodium butryate in no time.  So...

No-Entry-Barrieer Yamanaka Factor Modulators/Emulators

Oct3/4 : No idea, I'll be back.

Sox1/2 :  No idea, I'll be back.

cMyc :  Butryc acid.

Klf2/4 : No idea, I'll be back.

-------

We're not going to stop until everyone is growing biocompatible body parts in their basement, for recreational, medical, or other purpouses.  Because hacking, same as I've always dropped it down.

Re: IPSC-plus for the masses...

Klf4 Candidates!!

Okay, good news.  Some retardedly-named compound (CHIR99021), coupled with the lysine-specific demethylase inhibitor parnate, is a Klf4 (and Oct4) inducer.    Kenpaullone can sub for direct Klf4 activation alone.

https://doi.org/10.1073%2fpnas.0903860106
https://doi.org/10.1038%2fnbt1418

What's the common thread?  GSK3 inhibition!!  (err, glycogen synthesis kinase 3).

Could just be a coincidence.  But.... it still creates a  list of test candidates.

Naproxen

That friendly otc painkiller aleve, bane of stomachs and headaches alike?

https://www.ncbi.nlm.nih.gov/pubmed/23784744

Yeah.  It's on the list.

Curcumin

Yup.  Dat curry be vatgrowin' me new organs nao...

https://www.ncbi.nlm.nih.gov/pubmed/28579298

Resveratrol

https://www.ncbi.nlm.nih.gov/pubmed/28579298

Same ref.

Berberine

https://www.ncbi.nlm.nih.gov/pubmed/28579298

If grapes aren't good enough, try california poppy.

Lithium

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282483/

Punch bipolar.  Grow bipolar from bloodstain and their meds.  No problem!!

Now, the fact that gsk3 inhibitors keep tagging Klf4 could just be coincidence.  Or, it could be a sign.  It's still a reasonable lead to make vat-growing organs (or sex partners or clones)  a completely-unrestrictable homebrew affair.  Definitely worth at least testing.

I'll... be back with the rest soon, hombres-of-indeterminate-gender-or-species.  Still searching it up, writing it up, and hacking it out.  Take care!