Stem cell research uncovers importance of cell cycle

December 17, 2013 by April Reese Sorrow, University of Georgia

(Medical Xpress)—One of the biggest problems in stem cell research may not be a problem at all. Scientists have worried for years that stem cells grown in their labs were made up of many different kinds of cells, making them useless for stem cell therapies, but new research from the University of Georgia suggests they're not different cells, some are just more mature than others.

Amar Singh, postdoctoral associate in the Franklin College of Arts and Sciences, and Georgia Research Alliance Eminent Scholar of Molecular Cell Biology Stephen Dalton worked together to uncover the mystery about why stem cell populations are thought to be heterogeneous, or made up of a variety of different . They discovered the heterogeneity, or difference among the cells, is largely determined by the .

Their results were published Dec. 5 in the journal Stem Cell Reports.

"Since our study shows that heterogeneity may be a normal part of stem cell growth, this may not be that big of a deal anymore," said Singh, who is a researcher in the Franklin College department of biochemistry and molecular biology. "Also, since the cell cycle controls , seeing a certain level of heterogeneity in the cells you want to transplant may also be normal."

The idea that stem cells are heterogeneous, or that the cells making up a population are not all identical, emerged in the mid-2000s, and the reason has remained a mystery. Stem cells grow as a population of 1 to 2 million cells per culture dish because cells need to be surrounded by neighboring cells to survive. However, cells next to each other may be at different stages of development, which makes them appear like different cell types.

Stem cell transplants are used to assist in the regeneration of vital organs. Patients who suffer heart attacks may need a transplant of cardiomyocytes, a person with diabetes may benefit from a pancreatic cell transplant and liver disease patients can receive hepatic cells. The goal is to provide a transplant of uniform cells, or a homogeneous population. Until now, researchers would discount a heterogeneous cell population as unworthy for transplant.

A cell takes 18-24 hours to progress through the four stages of the cell cycle resulting in mitosis, or the division of the cell resulting in two identical cells. As turn into lineage cells, they don't shut down stem cell genes and turn on lineage genes. In fact, it is much more dynamic, the gene expression goes up and down as the cell cycle progresses.

"Now that we know that these developmental genes are more dynamic in their expression patterns as it relates to the cell cycle, we should be able to better evaluate cells that will be useful for cell-based therapies," Singh said.

Understanding the importance of the cell cycle in terms of gene development suggests the process should be taken into account in disease modeling and when testing drug effects.

"Since the cell cycle affects the expression of genes, it may be important to consider what phase of the cell cycle a particular cell is in to evaluate drug efficacy," Singh said.

Understanding the cell cycle's effect on the early stages of biological development offers new avenues for future research, including cancer research. Subtle differences in cancer cells may also be explained by the same phenomenon, as tumors are often thought of as heterogeneous.

"It turns out that developmental genes are often switched back on in cancers," Singh said. "Since these genes are controlled by the cell cycle, it may explain the heterogeneity seen here. Understanding how the cell cycle controls the heterogeneity in tumors will be critical for improved cancer treatments."

Explore further: How prostate cancer cells evolve

More information: Cell-Cycle Control of Developmentally Regulated Transcription Factors Accounts for Heterogeneity in Human Pluripotent Cells. "Amar M. Singh, James Chappell, Robert Trost, Li Lin, Tao Wang, Jie Tang, Hao Wu, Shaying Zhao, Peng Jin, Stephen Dalton. Stem Cell Reports 05 December 2013. DOI: 10.1016/j.stemcr.2013.10.009

Related Stories

How prostate cancer cells evolve

December 4, 2013
(Medical Xpress)—UCLA researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies. 

Paths not taken: Notch signaling pathway keeps immature T cells on the right track

November 23, 2013
One protein called Notch, which has well-known roles in the development of multiple tissues, plays an essential role in triggering T-cell development. Notch signaling induces expression of genes that promote the maturation ...

Scientists identify key regulator controlling formation of blood-forming stem cells

September 26, 2013
Stem cell scientists have moved one step closer to producing blood-forming stem cells in a Petri dish by identifying a key regulator controlling their formation in the early embryo, shows research published online today in ...

Study of 'sister' stem cells uncovers new cancer clue

September 26, 2013
Scientists have used a brand new technique for examining individual stem cells to uncover dramatic differences in the gene expression levels – which genes are turned 'up' or 'down'– between apparently identical 'sister' ...

Recommended for you

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.


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.