Windows bug-testing software cracks stem cell programs

SOFTWARE used to keep bugs out of Microsoft Windows programs has begun shedding light on one of the big questions in modern science: how stem cells decide what type of tissue to become.

Not only do the results reveal that cellular decision-making is nowhere near as complicated as expected, they also raise hopes that the software could become a key tool in regenerative medicine.

"It is a sign of the convergence between carbon and silicon-based life," says Chris Mason, a regenerative medicine specialist at University College London. "World-class stem cell scientists and a world-class computer company have found common ground. It is work at such interfaces that brings the big breakthroughs."

Stem cells are the putty from which all tissues of the body are made. That means they have the potential to repair damaged tissue and even grow into new organs.

Embryonic stem cells hold particular promise as they can either renew themselves indefinitely or differentiate into any kind of cell in the body a property known as pluripotency.

The process that sets a stem cell on the path to either self-renewal or differentiation was thought to be a highly complex web of genetic and environmental interactions. That web is known as the interactome.

Embryonic stem cells are currently being trialled as a way to restore vision and treat spinal injury. But these trials, and others in the pipeline, are hampered by the fact that no one really knows what determines the fate of any particular stem cell. Today's techniques for making a stem cell differentiate into a certain tissues are hit-and-miss, says Mason.

What's needed is a more deterministic, reliable method, says Sara-Jane Dunn, a computational biologist at Microsoft Research in Cambridge. One approach is to frame the problem in the language of computation. The genetic and environmental cues that determine the cell's fate can be thought of as inputs, with the cell itself as the processor, Dunn says.

Stem cells' capacity to renew themselves is the simplest of the two possible paths out of the pluripotent state. To find the program behind this, Dunn, along with stem cell scientists Graziano Martello at the University of Padua in Italy, and Austin Smith at the University of Cambridge, tried to isolate the genetic and environmental processes at work in mouse embryonic stem cells.

They used a technique pioneered at Smith's lab that uses cultures of various inhibitory proteins to keep embryonic stem cells continually renewing themselves rather than differentiating into other cells. The team immersed the stem cells in four different types of these cultures and analysed which genes they expressed in which environment, and to what extent.

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Windows bug-testing software cracks stem cell programs