Acid Shock Makes Stem Cells

UPDATE: Unfortunately the results of this study were found to involve fraudulent data. An update on the finding is reported here.

It was long established that vertebrate development is a one-way path. Like time’s arrow, cells differentiate by losing their old “pluripotency” (multiple possible fates). There were glimmers of the opposite, such as the partial loss of differentiation observed in cancer cells. But such phenomena always involved really bad results, such as uncontrolled growth. Fate maps such as this one could predict where embryonic cells would go, and what their differentiation would form. In certain organisms, such as the worm Caenorhabditis, nearly every cell of the early embryo has a predestined fate.

But in recent years, reports of “adult stem cells” suggest that a surprisingly small number of genes in the cells of a mature organism could direct a reversal of differentiation, restoring an at least partly pluripotent state. Now, it is startling to hear that something as simple as an acid shock can convert an adult cell into a cell with embryonic potential. Acid shock is something that my students study all the time in bacteria–that is our business, acid-shocking E. coli, and observing it adapt. The acid shocking of the mouse cells to form “stem cells” looks surprisingly similar.

In this case, apparently pH 5.7 is enought of an acid shock to do the trick. How this works is unknown, although not entirely unprecedented; for example, fertilization of sea urchin eggs involved an acid change. And viral infections, such as the uptake of influenza virus, involve acid-mediated fusion events to get the virus into the cytoplasm. More interestingly, a neural transformation event in salamanders has been triggered by acid treatment.

What is amazing in Obogata’s work is that the acid-induced cells could actually be put into a mouse embryo and observed to form all different parts of the new embryonic mouse (see above). The introduced cells could be observed because their genes express GFP (green fluorescent protein)–a molecule that Kenyon students use to track pH of single E. coli cells. The acid-shocked cells appear pluripotent, to the point of forming placental tissue as well as embryo tissues.

What does all this mean for our concepts of the embryo and adult? Perhaps the fertilized egg and embryo become less special, if any adult cell can become an embryo? Or do we have to treat every human cell as a potential human being.