October 25, 2020

The Niche

Knoepfler lab stem cell blog

Jaenisch’s new Cell paper on iPS cells 2.0: a helpful, brief analogy

Yesterday I just did a post on Jaenisch’s very dense, interesting Cell paper on iPS cells, but understandably it still is confusing to many people.

I think I’ve come up with a helpful analogy.

Imagine you are on a plane (this is your fibroblast cell) and the pilot dies.

You have to fly the jumbo jet plane and land it (turn it into an iPS cell), but you are not a pilot.

You go up to the cockpit and are confronted with hundreds of buttons.

Which is the right one?

Who knows.

You start pressing all the buttons randomly. Lights come on, landing gear comes up and down. The flaps go up and down. Oxygen masks fly around. The plane jerks around. Passengers freak out. Chaos.

But finally you hit that right button, the autopilot button! Suddenly the plane starts to behave in an orderly fashion to prepare for landing.

In this hypothetical scenario probably a lot of the time the plane crashes and you all die. This is equivalent to “bad” outcomes during the cellular reprogramming process of partially reprogrammed cells, dead cells, and cancer cells arising instead of iPS cells. But on rare occasions you push the right button soon enough and do not push a deadly button (dump all fuel, etc) too soon so that you land safely.

This is one way to view the reprogramming process. It’s chaos at the beginning until the right button, the autopilot button for induced pluripotency in the form of Sox2 (at least in the case of this Jaenisch paper) gets pushed.

Then the autopilot takes over and orderly steps follow. You get iPS cells.

So in this way of thinking if you can make the first chaotic stage of iPS cell formation more structured and less random, you should be able to make iPS cells a lot more easily and perhaps the quality might improve too.

By analogy our forced volunteer pilot filling in for the dead trained one on the jumbo jet might already have flown a small putt-putt plane so while she might still make a few mistakes, there were be less chaos.

Make sense?

If you are a stickler for conceptual modeling based on energy states you might say a plane taking off is a better analogy for iPS cell formation than a plane landing, but I like the landing scenario better in some ways as it indicates how high the stakes are.