Scientists discover a way to create specialized cells more efficiently

July 29, 2016 by Sarah C.p. Williams
Neural cells produced from human pluripotent stem cells in the presence of a metabolite called alpha-ketoglutarate. Credit: UCLA Broad Stem Cell Research Center

Researchers at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered that a metabolic molecule called alpha-ketoglutarate helps pluripotent stem cells mature early in the process of becoming adult organs and tissues. The findings, published online today in the journal Cell Metabolism, could be valuable for scientists working toward stem cell–based therapies for a wide range of diseases.

Pluripotent have the ability to create any specialized cell in the body, such as skin, bone, blood or —a process called differentiation. Because of that ability, scientists are studying to determine whether they can generate healthy tissues that could be used to treat people with conditions ranging from Alzheimer's disease to blindness.

But to coax pluripotent stem cells into any desired cell type, scientists have to find the right conditions and mixture of molecules to add to the stem cells to promote differentiation.

"One of the biggest challenges in our field has been to use pluripotent stem cells to efficiently create specialized cells that can carry out specific functions in the body," said Dr. Michael Teitell, the study's senior author and a member of the Broad Stem Cell Research Center. "Our findings may help overcome that challenge and let scientists more easily create cells to treat disease."

As they differentiate into specialized cells, pluripotent stem cells undergo a shift in their metabolism, and they begin converting sugars to energy more efficiently. Teitell and his colleagues wondered whether molecules involved in metabolism, or metabolites, might be more than just byproducts of this shift, and might actually help the stem cells differentiate.

Scientists discover a way to create specialized cells more efficiently
Dr. Mike Teitell and Tara TeSlaa. Credit: UCLA Broad Stem Cell Research Center

To find out, they added a metabolite called alpha-ketoglutarate to a mixture of molecules that normally turns human pluripotent stem cells into nervous system cells. Within the first four days of the experiment, 5 percent to 40 percent more cells differentiated into than usual. The researchers saw similar results when they added alpha-ketoglutarate to other cocktails of molecules that are used to produce other cell types. The alpha-ketoglutarate, they found, sped up the process of differentiation.

"On its own, alpha-ketoglutarate probably wouldn't promote differentiation, but when you add it to other factors that propel the creation of specialized cells, it seems to accelerate this process," said Tara TeSlaa, first author of the new study and a graduate student in Teitell's lab.

Since alpha-ketoglutarate is known to change how genes are regulated by removing methyl chemical groups from the DNA in a cell, Teitell and TeSlaa suspected that the molecule was helping cells turn off genes related to pluripotency and turn on genes related to more efficient differentiation.

To test that theory, they added another chemical, succinate, to the stem cell mixtures. Succinate blocks the same DNA demethylation chemical reaction that alpha-ketoglutarate promotes. Indeed, the addition of succinate caused the stem cells to differentiate slower and less efficiently, which provided further evidence that alpha-ketoglutarate works by acting on genes.

"Until very recently, metabolites have been overlooked as a way to help pluripotent stem cells differentiate," said Teitell, professor of pathology and laboratory medicine at the UCLA David Geffen School of Medicine. "This work helps to change that view."

Teitell and TeSlaa think that others in the field will build upon their study by testing whether alpha-ketoglutarate improves a variety of processes. They are planning follow-up studies to find out exactly which genes alpha-ketoglutarate regulates and how it can promote differentiation in some situations.

Explore further: Starving stem cells may enable scientists to build better blood vessels

Related Stories

Discovery links shift in metabolism to stem cell renewal

December 10, 2014

Stem cells in early embryos have unlimited potential; they can become any type of cell, and researchers hope to one day harness this rejuvenating power to heal disease and injury. To do so, they must, among other things, ...

Research advance may lead to new treatments for glaucoma

March 22, 2016

Researchers have developed a tool to not only model the underlying disease mechanisms of glaucoma, but also to help discover and test new pharmacological strategies to combat the neurodegeneration that occurs in patients ...

Changing pluripotent stem cells to differentiated cells

March 9, 2016

Stem cells are an effective tool for repairing or replacing damaged or diseased tissues, but only if they can be reliably developed from their flexible 'pluripotent' state into a mature 'differentiated' state. A*STAR researchers ...

Recommended for you

Gene editing in the brain gets a major upgrade

October 19, 2017

Genome editing technologies have revolutionized biomedical science, providing a fast and easy way to modify genes. However, the technique allowing scientists to carryout the most precise edits, doesn't work in cells that ...

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.