Nav: Home

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

November 14, 2017

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 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 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 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.

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

"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 cells as they exist in their native state in the tissue."
-end-
Other Stanford authors of the study are postdoctoral scholars Antoine de Morree, PhD, and Ingrid Egner, PhD; and graduate student Jamie Brett.

The research was supported by the Glenn Foundation for Aging Research, the Muscular Dystrophy Association, the National Institutes of Health (grants AG036695, AG23806 and AG047820), the California Institute for Regenerative Medicine and the Department of Veterans Affairs.

Stanford's Department of Neurology and Neurological Sciences also supported the work.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Stanford Children's Health. For information about all three, please visit http://med.stanford.edu.

Print media contact:

Krista Conger
650-725-5371
kristac@stanford.edu

Broadcast media contact:

Margarita Gallardo
650-723-7897
mjgallardo@stanford.edu

Stanford University Medical Center

Related Stem Cells Articles:

A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Approaching a decades-old goal: Making blood stem cells from patients' own cells
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
New research finds novel method for generating airway cells from stem cells
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Mature heart muscle cells created in the laboratory from stem cells
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
Mutations in bone cells can drive leukemia in neighboring stem cells
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
Scientists take aging cardiac stem cells out of semiretirement to improve stem cell therapy
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
Purest yet liver-like cells generated from induced pluripotent stem cells
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Stem cells from diabetic patients coaxed to become insulin-secreting cells
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.

Related Stem Cells Reading:

Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)

Stem cells are the repair cells of your body.  When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.

Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work,... View Details


Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)

Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the... View Details


Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)

Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how... View Details


Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)

The first authoritative yet accessible guide to this controversial topic

Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.

Explains the differences between adult stem cells and embryonic/umbilical... View Details


The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)

The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures... View Details


Stem Cells: Promise and Reality
by Lygia V Pereira (Author)

Stem Cells: Promises and Reality will tell you everything you have always wanted to know about stem cells, but could not understand the field from elsewhere. Stem cells are the great therapeutic promise of the century, and this evolving field of research and medicine brings with it many legal, ethical and psychological issues that must be discussed by society as a whole. Written so as to be accessible to general readers as well as specialists, this book explains what stem cells are, and the different aspects of stem cell research and applications. The book will enable the reader to understand... View Details


Stem Cells Are Everywhere
by Irv Weissman MD (Author)

An engaging introduction to stem cells for young scientists
 
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it. View Details


Stem Cells: A Short Course
by Rob Burgess (Author)

Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem... View Details


Essentials of Stem Cell Biology, Third Edition
by Robert Lanza (Editor), Anthony Atala (Editor)

First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest... View Details


The Science of Stem Cells
by Jonathan M. W. Slack (Author)

Introduces all of the essential cell biology and developmental biology background for the study of stem cells 

This book gives you all the important information you need to become a stem cell scientist. It covers the characterization of cells, genetic techniques for modifying cells and organisms, tissue culture technology, transplantation immunology, properties of pluripotent and tissue specific stem cells and, in particular, the relevant aspects of mammalian developmental biology. It dispels many misconceptions about stem cells—especially that they can be miracle... View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Simple Solutions
Sometimes, the best solutions to complex problems are simple. But simple doesn't always mean easy. This hour, TED speakers describe the innovation and hard work that goes into achieving simplicity. Guests include designer Mileha Soneji, chef Sam Kass, sleep researcher Wendy Troxel, public health advocate Myriam Sidibe, and engineer Amos Winter.
Now Playing: Science for the People

#448 Pavlov (Rebroadcast)
This week, we're learning about the life and work of a groundbreaking physiologist whose work on learning and instinct is familiar worldwide, and almost universally misunderstood. We'll spend the hour with Daniel Todes, Ph.D, Professor of History of Medicine at The Johns Hopkins University, discussing his book "Ivan Pavlov: A Russian Life in Science."