Stem cells express genes differently in the lab dish than in the body, study finds

November 14, 2017, Stanford University Medical Center
Credit: CC0 Public Domain

Stem cells in the body have a significantly different gene-expression profile than do the same cells when they're isolated in a lab dish, according to researchers at the Stanford University School of Medicine.

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

"The cells in the animal clearly differ from those that are removed for study," said Thomas Rando, MD, PhD, professor of neurology and neurological sciences. "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."

A study describing the research will be published Nov. 14 in Cell Reports. Rando, the director of Stanford's Glenn Center for the Biology of Aging, is the senior author. Postdoctoral scholar Cindy van Velthoven, PhD, is the lead author.

New technology

Previous studies of stem cell gene expression have been largely based on cells that had been removed from their native environment within an animal and purified through a process called fluorescence-activated cell sorting, or FACS. Researchers then studied the function, biology and RNA content of the isolated cells.

In contrast, Rando and his colleagues used a new technology that allowed them to specifically label RNA molecules at the moment of their birth in muscle stem cells in mice. These molecules could then be rapidly extracted for study, in contrast to the several hours it can take to isolate whole stem cells from an animal. This approach allowed them to distinguish the patterns of gene expression in vivo from those observed in stem cells that have been isolated before analysis of their RNA.

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 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.

"Historically, we've thought of quiescence as an 'everything off,' or dormant, state," said Rando. "But our work has shown that the reality is quite different. Not only have we been missing transcripts that are present in vivo, but we are also puzzled as to why so many transcripts that are made in vivo are not made into proteins. It's possible that this is one way the cells stay ready to undergo a rapid transformation, either by blocking degradation of RNA or proteins or by swiftly initiating translation of already existing RNA transcripts."

Effects of cell isolation

The researchers found that isolated cells make large numbers of RNA molecules known to be involved in cellular stress and in cellular proliferation. Conversely, stem cells in the body make more RNAs involved in maintaining the quiescent state, in which they exist until called upon to make new muscle fibers.

The researchers additionally found that the process of isolating whole 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.

Rando and his colleagues expect that the new RNA labeling technique will be used by many other researchers studying .

"It's so important to know what we are and are not modeling about the state of these cells in vivo," said Rando. "Are we modeling it correctly when we look at stem cells isolated by FACS? This study will have a big impact on how researchers in the field think about understanding the characteristics of stem as they exist in their native state in the tissue."

Explore further: Autophagy helps fast track stem cell activation

Related Stories

Autophagy helps fast track stem cell activation

October 14, 2014
Researchers from Stanford University School of Medicine have discovered a link between a protective mechanism used by cells and the activation of muscle stem cells. Cells use autophagy to recycle cellular "building blocks" ...

Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

February 8, 2017
Adding just the right mixture of signaling molecules—proteins involved in development—to human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

Protein primes mouse stem cells to quickly repair injury, study finds

April 18, 2017
Like drag car racers revving their engines at the starting line, stem cells respond more quickly to injury when they've been previously primed with one dose of a single protein, according to a study from the Stanford University ...

Scientists trigger muscle stem cells to divide

February 23, 2012
(Medical Xpress) -- A tiny piece of RNA plays a key role in determining when muscle stem cells from mice activate and start to divide, according to researchers at the Stanford University School of Medicine. The finding may ...

Study identifies cell-cycle phase that primes stem cells for action

May 26, 2014
Resting, adult stem cells of many types of tissues enter a reversible "alert" phase in response to a distant injury, according to a study in mice by researchers at the Stanford University School of Medicine.

Recommended for you

Team develops new way to grow blood vessels

August 17, 2018
Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed ...

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Obesity, infertility and oxidative stress in mouse egg cells

August 16, 2018
Excessive body fat is associated with negative effects on female fertility and pregnancy. In mice, maternal obesity impairs proper development of egg precursor cells called oocytes. In a recent paper published in Molecular ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

This matrix delivers healing stem cells to injured elderly muscles

August 15, 2018
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method ...

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.