Identity Matters

How does a stem cell know to remain a stem cell and not change into something as interesting as, say, a neuron? Using stem cells for cell replacement therapies—either transplanting them or activating those already in a patient’s body—requires understanding how stem cells follow such identity instructions.

Lab mouse
(Photo/Rama).

Researcher Nick Gaiano of the Johns Hopkins Institute for Cell Engineering has found part of the answer through his work on the neural stem cells in embryonic mouse brains. Such work could ultimately help scientists isolate stem cells for therapeutic uses from the human brain as well as from other body tissues.

Gaiano’s team looked at the gradual maturation process through which stem cells become adult tissue. During brain development, some neural stem cells turn into progenitor cells, a group that mostly ages into neurons. Other cells, however, remain true neural stem cells, which can form all major brain cell types.

A molecular communications system called the Notch signaling pathway appears to regulate whether stem cells change or stay the same. To study the process in greater detail, the Hopkins team created genetically engineered mice embryos that glowed green when a certain protein—CBF1—was activated by Notch.

The Hopkins researchers found that when neural stem cells began to change into progenitor cells, the green light went off, implying that the protein was no longer active within them. On the other hand, true neural stem cells continued to glow.

To test whether CBF1 was actually serving as a switch, the researchers destroyed the protein in some neural stem cells. They began to differentiate. Activating the protein in more mature cells, however, did not shift them back to their original form.

Another subsequent study with similar results causes Gaiano to believe that this protein signaling may work as a “switch” that helps distinguish stem cells from progenitors in many different tissues.

 “The Notch signaling pathway plays a role in virtually every stem cell population in our bodies: in blood stem cells, in skin stem cells, in muscle stem cells,” he says. “It also plays a role in many cancers, so understanding how it works is of great therapeutic importance.”

--Linell Smith