A drug-like molecule called Wnt can be substituted for the cancer gene c-Myc, one of four genes added to adult cells to reprogram them to an embryonic-stem-cell-like state, according to Whitehead researchers. Researchers hope that such embryonic stem-cell-like cells, known as induced pluripotent (IPS) cells, eventually may treat diseases such as Parkinson’s disease and diabetes.
Demonstrated in mice, the elimination of c-Myc represents an important step in creating IPS cells in a manner that in the future may be applied to human therapeutics.
“This is a good sign for the possible replacement of the other three genes used to reprogram cells,” says Ruth Foreman, a MD/PhD student in the lab of Whitehead Member Rudolf Jaenisch and a lead co-author on the paper, published online in Cell Stem Cell on August 6. The other lead co-authors are Alex Marson, an MD/PhD student in the labs of Jaenisch and Whitehead Member Richard Young, and Brett Chevalier, a research scientist in the Young lab.
“IPS cells hold great potential for future medicine, but we must learn how to generate these cells in a manner that is safe for clinical therapies,” says Young, who is also a professor of biology at Massachusetts Institute of Technology. “This advance in reprogramming is one key step toward that goal,”
Currently, IPS cells can be created by reprogramming adult cells through the use of viruses to transfer four genes (Oct4, Sox2, c-Myc and Klf4) into the cells’ DNA. The activated genes then override the adult state and convert the cells to embryonic-like IPS cells.
However, this method poses significant risks for potential use in humans.
First, the viruses employed in the process, called retroviruses, are associated with cancer because they insert DNA anywhere in a cell’s genome, thereby potentially triggering the expression of cancer-causing genes, or oncogenes. Second, c-Myc is a known oncogene whose overexpression can also cause cancer. For IPS cells to be employed to treat human diseases such as Parkinson’s, researchers must find safe alternatives to reprogramming with retroviruses and oncogenes.
Earlier research has shown that c-Myc is not strictly required for the generation of IPS cells. However, its absence makes the reprogramming process time-consuming and highly inefficient.
To bypass these obstacles, the Whitehead researchers replaced c-Myc and its retrovirus with a naturally occurring signaling molecule called Wnt3a. When added to the fluid surrounding the cells being reprogrammed, Wnt3a promotes the conversion of adult cells into IPS cells.
“We’re not sure if the Wnt molecule is doing the same thing as c-Myc or complementing c-Myc’s activity,” says Chevalier. “But it does increase stem cell growth similar to c-Myc.”
“This is a good start toward using external cues instead of genetic manipulation to reprogram cells,” says Marson. “But we still need to eliminate the need for retroviruses for the three other genes.”
Although the technique is promising in mouse cells, its potential applications in humans have not been studied, emphasizes Jaenisch, who is also a professor of biology at MIT. “Is the same pathway acting in the human system and can Wnt molecules be used to reprogram human cells?” he asks. “We don’t know, but I think those are very important questions to investigate.”
This research was supported by the National Institutes of Health.
Rudolf Jaenisch and Richard Young’s primary affiliations are with Whitehead Institute for Biomedical Research, where their laboratories are located and all their research is conducted. Jaenisch and Young are also professors of biology at Massachusetts Institute of Technology.Full citation:
Alexander Marson (1,2), Ruth Foreman (1,2), Brett Chevalier (1), Michael Kahn (3,4), Richard A. Young (1,2), Rudolf Jaenisch (1,2).1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
4. Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.
Cristin Carr | Newswise Science News
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences