Many paths, few destinations: How stem cells decide what ...( How does a stem cell decide what spe...)

How does a stem cell decide what specialized identity to adopt or simply to remain a stem cell? A new study suggests that the conventional view, which assumes that cells are instructed to progress along prescribed signaling pathways, is too simplistic. Instead, it supports the idea that cells differentiate through the collective behavior of multiple genes in a network that ultimately leads to just a few endpoints just as a marble on a hilltop can travel a nearly infinite number of downward paths, only to arrive in the same valley.

The findings, published in the May 22 issue of Nature, give a glimpse into how that collective behavior works, and show that cell populations maintain a built-in variability that nature can harness for change under the right conditions. The findings also help explain why the process of differentiating stem cells into specific lineages in the laboratory has been highly inefficient.

Led by Sui Huang, MD, PhD, a Visiting Associate Professor in the Childrens Hospital Boston Vascular Biology Program (now also on the faculty of the University of Calgary), and Hannah Chang, an MD/PhD student in Childrens Vascular Biology Program, the researchers examined how blood stem cells decide to become white blood cell progenitors or red blood cell progenitors.

They began by examining populations of seemingly identical blood stem cells, and found that a cell marker of stemness, a protein called Sca-1, was actually present in highly variable amounts from cell to cell in fact, they found a 1,000-fold range. One might think that low Sca-1 cells are simply those cells that have spontaneously differentiated. However, when Huang and Chang divided the cells expressing low, medium and high levels of Sca-1 and cultured them, each descendent cell population recapitulated the same broad range of Sca-1 levels over nine days or more, regardless of what levels they started with.

We then asked, are these cells also biologic
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