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Adult stem cells act differently in the body than when isolated for study, say Stanford researchers

I think it's fair to say that most people act at least somewhat differently in public than they do in the privacy and comfort of their own homes. I don't walk around in my pajamas at the grocery store or spend much time fussing over my hair when I don't plan to leave the house, for example. Now it appears that adult stem cells exercise similar location-specific judgment calls, and that these differences may call into question the results of previous studies of these cells.

One key way to understand how any cell functions is to eavesdrop on its internal monologue. What genes does it express and when? What proteins does it make? To intercept these messages, researchers usually isolate the cells for study in a laboratory dish. But now, Stanford neurologist and stem cell expert Thomas Rando, MD, PhD, together with postdoctoral scholar Cindy van Velthoven, PhD, have found that the very process of isolating the cells (using a process called fluorescence-activated cell sorting, or FACS) significantly changes their gene expression patterns.

They published their results today in Cell Reports. 

As I describe in our release:

The research suggests that any conclusions about stem cell function based on studies of isolated stem cells may now need to be reconsidered in light of the fact that the cells’ biology changes during isolation. In particular, the researchers found that levels of certain RNA molecules increased when stem cells were isolated, whereas the levels of many other RNA molecules decreased.

The researchers used a new technique to label RNA molecules within mice at the moment of their creation in muscle stem cells. They then could quickly isolate the RNA and compare the expression patterns of cells within the body, or 'in vivo' cells, with that of cells that had first been isolated and then analyzed.

Like other adult stem cells, muscle stem cells appear to spend most of their lives resting quietly, waiting to be called into action to repair damage from injury or trauma. But there's a lot going on underneath the hood during this so-called quiescent state.

From our release:

The results confirmed what previous research in Rando’s laboratory has shown: Despite their seemingly sleepy lifestyle, muscle stem cells are actually hotbeds of activity concealed by a tranquil outer membrane. The researchers were particularly surprised to learn that [within the animal] many of the RNAs made by the muscle stem cells in vivo are either degraded before they are made into proteins, or they are made into proteins that are then rapidly destroyed — a seemingly shocking waste of energy for cells that spend most of their lives just cooling their heels along the muscle fiber.


The researchers additionally found that the process of isolating whole muscle stem cells for study caused some important RNA molecules to be degraded, rendering them undetectable in previous studies. These findings further support the notion that this quiescent state is not one of dormancy, but one of active regulation and controls — controls that are no longer needed once the cells are awakened to begin the process of tissue repair.

As Rando, who directs Stanford’s Glenn Center for the Biology of Aging, explained, “The cells in the animal clearly differ from those that are removed for study. It’s likely that some of these notable differences will skew our view of what the quiescent state entails for many types of adult stem cells. We and other researchers will need to rethink about how to profile stem cells in a way that accurately reflects their in vivo state.”

Previously: How to encourage muscle stem cells to replace missing muscle? A familiar home, a few friends and some healthy exercise, Speeding healing with a dose of a single protein and Coaxing muscles to heal with less scarring could improve aging, muscular dystrophy treatments  
Photo by National Institute of Arthritis and Musculoskeletal and Skin Diseases

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