An embryo starts out as just a single cell. It’s not long before it divides into two cells, then four, then eight, and so on — a process marked by rapid growth, in which these early, unspecialized cells proliferate wildly to start building all the tissues of the body. As development proceeds, these embryonic (and later fetal) stem cells become more specialized, differentiating into the precursors of various cell lineages, which in turn give rise to more mature cells: blood cells, nerve cells, muscle cells, intestinal cells. Major functional changes in these tissues continue to take place after birth, as the organism adapts to life outside the uterus, for the first time using its lungs to breathe air and its digestive system to process food.

A few cell populations retain some of that early plasticity as adult stem cells, helping both to maintain tissues on a day-to-day basis and to heal wounds. In recent years, moreover, it’s become clear that those aren’t the only cells that stay flexible: Sometimes, when the repair process calls for it, more specialized cells can take a few steps back, or “de-differentiate,” to re-enter a stemlike state, too.

But new results suggest that that plasticity may go even deeper than scientists have thought. Three research teams have observed that during tissue regeneration, the typical solutions offered by adult stem cells (and the de-differentiated cells resembling them) aren’t enough. Instead, the cells of the damaged tissue turn the clock back all the way to a more fetal state, tapping into the proliferative power that once characterized development — and a program thought to have long gone silent.

Atom Bombs and Self-Renewing Cells

In the early 1900s, scientists theorized that the specific blood cell types they’d learned to distinguish from one another under a microscope — red blood cells, white blood cells and platelets — came from a common, more primitive source: a stem cell. But it wouldn’t be until the 1950s and ’60s that researchers could offer definitive proof of their existence and begin to delineate their unique properties.

The discovery of the first stem cells came about indirectly from the atomic bombings of Hiroshima and Nagasaki in 1945. Medical workers observed that exposure to radiation caused a precipitous drop in the survivors’ white blood cell counts, and experiments in mice showed that bone marrow transplants could offset those losses. Work over the following decades gradually revealed why: A population of cells in the marrow could both self-renew and differentiate into various, more specialized blood cell lineages. These were the blood-making stem cells.

They departed from the behavior of more specialized cells in several key ways. When a differentiated cell divided, it produced two copies of itself — and depending on the cell type, the number of times it could do so was limited. That wasn’t the case with the stem cells isolated from the bone marrow. When they divided, they did so over extremely long periods of time, in a process known as proliferation. Moreover, those divisions were asymmetric: Each stem cell produced not only a copy of itself but also a daughter cell fated to become a specific type of blood cell. For those daughter cells that gained a differentiated identity, there was generally no going back.