Ohio State University researchers at the Wexner Medical Center in Columbus, Ohio have collaborated with 26 other researchers from such fields as engineering, science, and medicine to create a fingernail sized chip that can be placed on the skin to force it to generate other kinds of tissues (article by JoAnne Viviano from the Columbus Dispatch, August 8, 2017).
Wow! This is my last alma mater! Kudos to all involved in this amazing project!
Hmmm…at first glance, this research appears to fly in the face of what I have said in the past regarding cellular differentiation, i.e., that’s it’s irreversible because the composition of the DNA changes and information is permanently lost. However, when hypotheses are challenged by data, the appropriate thing to do is adjust them accordingly. I did this quite a while back. Let me explain:
When an egg is fertilized by a sperm it generates a new organism that is totipotent., i.e., a cell with all the genetic potential to produce every tissue in the body as well as extraembryonic membranes. As time passes and tissues begin to form, this totipotency is eroded for each individual cell produced. One of the main reasons for this is that DNA information gets lost in the process. However, the DNA that is lost is not the same DNA for every kind of cell: Cells destined to become skin cells lose DNA that is different from cells destined to become some other kind of tissue. As the cells continue to differentiate, they lose progressively more and more DNA until they become fully differentiated. A textbook example of this is in the generation of white blood cells like lymphocytes. However, more subtle kinds of DNA loss may also be occurring in all kinds of cells during differentiation.
So therein, lies the kicker: If cellular differentiation results in permanent losses of DNA, how can scientists take skin cells and turn them into other kinds of tissues? Well, there is another process that facilitates cellular differentiation that I will call DNA sequestration. This involves something called heterochromatin which I have talked about before.
Instead of thinking of chromosomal DNA as one long continuous thread, visualize it in another way: Imagine that you placed an order to Amazon in order to build a certain kind of cell. When you get the box at your door and take it inside, you open it up and find a set of instructions you will need to build your cell. After reading the instructions carefully, you begin to follow them to a tee. There are all kinds of boxes inside the larger box, so you begin to take them and stack them neatly on the floor. The manufacturers of the “cell” have found it easier to just package everything together rather than send you only the stuff you need to make your favorite cell, so some of the boxes aren’t really needed for what you want to do. You set them aside and continue opening up the boxes you actually need. When these boxes are opened up, you find (guess what?), more boxes! Of course, some of these boxes aren’t needed either so you set them aside and go about your business. Finally you get to the motherlode and begin assembling your cell. This requires removing packing material and putting pieces together with glue, nuts and bolts. Some of the pieces have to be trimmed from the packaging material. Finally, you complete your masterpiece!
Oops! What happened? You read the wrong instructions! You built the wrong “blankity blank” cell! You go outside to vent your anger and frustration lest you kick a box inadvertently down the hallway. Don’t smoke a cigarette, they’re not good for you. Finally, you recuperate in your own healthy way and go back inside to survey the damage. Hmmm.. the instructions you followed were actually for a completely different kind of cell. Thanks, Amazon!
So what to do? Suddenly, an idea sparks within your brain. The boxes you really needed are still unopened. Maybe there is a way to salvage your project after all! You go online, tell Amazon what you think of their instructions, they apologize and send you a link to the correct instructions which you promptly print out. You begin by opening up other boxes which are applicable to the cell type you wanted in the first place. Soon, you have your cell in place and prepare to “fire up” the engine. You heard me right: Your cell is a finely tuned engine that actually generates a product you can sell. You plug her into the wall and voilà: She starts to smoke, groan, and heat up. You quickly unplug the thing before you start a fire. What happened? Well, you forgot about the other engine you created to make the wrong cell. It’s screwing everything up because they are both on the same circuit board and can interact with each other! So you disassemble the first cell as best you can and stuff it back into its boxes so it won’t interfere with the second one. It’s not perfect, but at least it works now.
So what happens in a skin cell when it is forced to convert into another kind of cell? A chimera or hybrid cell is created with two active compartments. If one of these compartments is not deactivated, the cell will go nuts trying to figure out which tissue to become. It will probably randomly deactivate one or the other compartments as it reproduces itself, generating a population of both kinds of cells. This is why cloning animals from stem cells has been so difficult to achieve. One possible way to eliminate the offending cell would be to use a selection process that either kills it off or prevents it from reproducing.
That’s my best guess for now. This is a very exciting, dynamic field of study. If you want to do “dry” research on this, by all means go for it and let me know what you learn.