A team of researchers from the University of California, San Diego School of Medicine and the Salk Institute for Biological Studies in La Jolla have developed a safe strategy for reprogramming cells to a pluripotent state without use of viral vectors or genomic insertions.
Their studies reveal that these induced pluripotent stem cells (iPSCs) are very similar to human embryonic stem cells, yet maintain a "transcriptional signature." In essence, these cells retain some memory of the donor cells they once were.
The study, led by UCSD Stem Cell Program researcher Alysson R. Muotri, assistant professor in the Departments of Pediatrics at UCSD and Rady Children's Hospital and UCSD's Department of Cellular and Molecular Medicine, will be published online in PLoS ONE on September 17.
"Working with neural stem cells, we discovered that a single factor can be used to re-program a human cell into a pluripotent state, one with the ability to differentiate into any type of cell in the body" said Muotri. Traditionally, a combination of four factors was used to create iPSCs, in a technology using viral vectors – viruses with the potential to affect the transcriptional profile of cells, sometimes inducing cell death or tumors.
In addition, while both mouse and human iPSCs have been shown to be similar to embryonic stem cells in terms of cell behavior, gene expression and their potential to differentiate into different types of cells, researchers had not achieved a comprehensive analysis to compare iPSCs and embryonic stem cells.
"One reason is that previous methodologies used to derive iPSCs weren't 'footprint free,'" Muotri explained. "Viruses could integrate into the genome of the cell, possibly affecting or disrupting genes."
"In order to take full advantage of reprogramming, it is essential to develop methods to induce pluripotency in the absence of permanent changes in the genome," added Fred H. Gage, PhD, a professor in the Laboratory for Genetics at the Salk Institute and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases.
By creating iPSCs from human neural stem cells without the use of viruses, the scientists learned something new. While the genetic transcriptional profile of the new iPSCs was closer to that of embryonic stem cells than to human neural stem cells, the iPSCs still carried a transcriptional "signature" of the original neural cell.
"While most of the original genetic memory was erased when the cells were reprogrammed, some were retained," said Muotri. He added that, in the past, it wasn't known if this was caused by the use of viral vectors. "By using a footprint-free methodology, we have shown a safe way to generate human iPSCs for clinical purposes and basic research. We've also raised an interesting question about what, if any, effect the 'memory retention' of these cells might have."
Additional contributors to the study include Gene W. Yeo, UCSD's Department of Cellular and Molecular Medicine and the UCSD Stem Cell Program; Osamu Kainohana and Martin Marsala, UCSD Department of Anesthesiology; and Maria C. N. Marchetto and Fred H. Gage, the Salk Institute for Biological Studies, La Jolla, CA.
The research was supported by startup funds from the UCSD Stem Cell Research Program, and by grants from the California Institute of Regenerative Medicine and The Lookout Fund Foundation.
Debra Kain | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy